Molecular pathways and therapeutic targets in lung cancer
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// Emma Shtivelman 1 , Thomas Hensing 2 , George R. Simon 3 , Phillip A. Dennis 4 , Gregory A. Otterson 5 , Raphael Bueno 6 , Ravi Salgia 7 1 Cancer Commons, Palo Alto, CA, United States of America 2 Northshore University Health System and University of Chicago, United States of America 3 MD Anderson Cancer Center, United States of America 4 Johns Hopkins University School of Medicine, United States of America 5 Ohio State University Comprehensive Cancer Center, United States of America 6 Brigham & Women’s Hospital, Harvard Medical School, United States of America 7 Department of Medicine, Section of Hematology/Oncology, University of Chicago, United States of America Correspondence: Emma Shtivelman, email: // Keywords : lung cancer, targeted therapy, immune therapy Received : March 18, 2014 Accepted : April 07, 2014 Published : April 08, 2014 Abstract Lung cancer is still the leading cause of cancer death worldwide. Both histologically and molecularly lung cancer is heterogeneous. This review summarizes the current knowledge of the pathways involved in the various types of lung cancer with an emphasis on the clinical implications of the increasing number of actionable molecular targets. It describes the major pathways and molecular alterations implicated in the development and progression of non-small cell lung cancer (adenocarcinoma and squamous cancer), and of small cell carcinoma, emphasizing the molecular alterations comprising the specific blueprints in each group. The approved and investigational targeted therapies as well as the immune therapies, and clinical trials exploring the variety of targeted approaches to treatment of lung cancer are the main focus of this review.
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The discovery of EGFR mutations in NSCLC launched the era of personalized medicine in advanced NSCLC and led to a shift in the therapeutic landscape from a one-size-fits-all approach to treatment selection based on molecular characteristics of tumors.
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From A decade of EGFR inhibition in EGFR-mutated non small cell lung cancer (NSCLC): Old successes and future perspectives (2015) · cites this paper as [2]
EGFR is a tyrosine kinase receptor activated upon binding to EGF and other growth factor ligands, triggering downstream pathways including RAS/MAPK, PI3K/Akt, and STAT that regulate DNA synthesis and proliferation.
“The Epidermal Growth Factor Receptor (EGFR) is a tyrosine kinase (TK) receptor that is activated upon binding to the Epidermal Growth Factor and other growth factor ligands, triggering several downstream pathways, including RAS/MAPK, PI3K/Akt and STAT that regulate different cellular processes, including DNA synthesis and proliferation.”
From A decade of EGFR inhibition in EGFR-mutated non small cell lung cancer (NSCLC): Old successes and future perspectives (2015) · cites this paper as [2]
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Karp, D. D., Paz-Ares, L. G., Novello, S., Haluska, P., Garland, L. L., Cardenal, F., Blakely, L. J., Eisenberg, P. D., Langer, C. J., Blumenschein, G. R., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.19.9331 · Cited by 260 · cited 1× · see citing works
“Anti-IGF1R antibody figitumumab (CP-751,871) in combination with carboplatinum-paclitaxel was tested in NSCLC with some initial promising results [135], but subsequent trials were discontinued because of futility and unacceptable toxicity.”
BackgroundRetractedPD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989 · see citing works
Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review
Wanchoo, R., Karam, S., Uppal, N. N., Barta, V. S., Deray, G., Devoe, C., Launay‐Vacher, V., Jhaveri, K. D., & on behalf of Cancer and Kidney International Network Workgroup on Immune Checkpoint Inhibitors (2017) · American Journal of Nephrology · doi:10.1159/000455014 · Cited by 15,314 · see citing works
Safety, activity, and immune correlates of anti–PD-1 antibody in cancer
Topalian, S. L., Hodi, F. S., Brahmer, J. R., Gettinger, S. N., Smith, D. C., McDermott, D. F., Powderly, J. D., Carvajal, R. D., Sosman, J. A., Atkins, M. B., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200690 · Cited by 12,628 · see citing works
Gefitinib or Carboplatin–Paclitaxel in Pulmonary Adenocarcinoma
Mok, T. S., Wu, Y.-L., Thongprasert, S., Yang, C.-H., Chu, D.-T., Saijo, N., Sunpaweravong, P., Han, B., Margono, B., Ichinose, Y., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0810699 · Cited by 8,261 · see citing works
Safety and activity of anti-PD-L1 antibody in patients with advanced cancer
Brahmer, J. R., Tykodi, S. S., Chow, L. Q. M., Hwu, W.-J., Topalian, S. L., Hwu, P., Drake, C. G., Camacho, L. H., Kauh, J., Odunsi, K., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200694 · Cited by 7,945 · cited 2× · see citing works
“Anti-PD-L1 antibody was also tested in several cancers, including melanoma, and objective responses were observed in 9 of 52 melanoma patients; the responses were durable [242].”
BackgroundGefitinib or Chemotherapy for Non–Small-Cell Lung Cancer with Mutated EGFR
Maemondo, M., Inoue, A., Kobayashi, K., Sugawara, S., Oizumi, S., Isobe, H., Gemma, A., Harada, M., Yoshizawa, H., Kinoshita, I., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa0909530 · Cited by 5,525 · see citing works
Identification of the transforming EML4–ALK fusion gene in non-small-cell lung cancer
Soda, M., Choi, Y. L., Enomoto, M., Takada, S., Yamashita, Y., Ishikawa, S., Fujiwara, S.-I., Watanabe, H., Kurashina, K., Hatanaka, H., et al. (2007) · Nature · doi:10.1038/nature05945 · Cited by 5,439 · cited 1× · see citing works
“The EML4-ALK oncogene is a fusion between echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK) [75].”
BackgroundFreeman, G. J., Long, A. J., Iwai, Y., Bourque, K., Chernova, T., Nishimura, H., Fitz, L. J., Malenkovich, N., Okazaki, T., Byrne, M. C., et al. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.7.1027 · Cited by 5,294 · cited 1× · see citing works
“Interactions between PD-1 and its ligands attenuate immune responses [241], and, in the context of cancer, serve to protect tumor cells from cytotoxic T cells.”
BackgroundIn Vivo Activation of the p53 Pathway by Small-Molecule Antagonists of MDM2
Vassilev, L. T., Vu, B. T., Graves, B., Carvajal, D., Podlaski, F., Filipovic, Z., Kong, N., Kammlott, U., Lukacs, C., Klein, C., et al. (2004) · Science · doi:10.1126/science.1092472 · Cited by 4,661 · cited 1× · see citing works
“Discovery of Nutlin-3, a promising inhibitor of MDM2 binding [176] energized the search for clinically active drugs.”
Background<i>MET</i> Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling
Engelman, J. A., Zejnullahu, K., Mitsudomi, T., Song, Y., Hyland, C., Park, J. O., Lindeman, N., Gale, C.-M., Zhao, X., Christensen, J., et al. (2007) · Science · doi:10.1126/science.1141478 · Cited by 4,496 · cited 1× · see citing works
“The other common mechanism of acquired resistance to EGFR tyrosine kinase inhibition involves amplification of RTK c-MET [41], a proto-oncogene that encodes a protein also known as hepatocyte growth factor receptor (HGFR),.”
BackgroundNivolumab plus Ipilimumab in Advanced Melanoma
Wolchok, J. D., Kluger, H., Callahan, M. K., Postow, M. A., Rizvi, N. A., Lesokhin, A. M., Segal, N. H., Ariyan, C. E., Gordon, R.-A., Reed, K., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1302369 · Cited by 4,230 · cited 1× · see citing works
“Nivolumab is currently in a number of trials in patients with NSCLC and two trials specifically for SQCC, either as a single agent or in combination with other targeted therapies or chemotherapy agents or ipilimumab NCT01454102 Combination of nivolumab and ipilimumab has already produced outstanding responses in patie…”
BackgroundZhou, C., Wu, Y.-L., Chen, G., Feng, J., Liu, X.-Q., Wang, C., Zhang, S., Wang, J., Zhou, S., Ren, S., et al. (2011) · The Lancet Oncology · doi:10.1016/s1470-2045(11)70184-x · Cited by 4,081 · see citing works
The landscape of somatic copy-number alteration across human cancers
Beroukhim, R., Mermel, C. H., Porter, D., Wei, G., Raychaudhuri, S., Donovan, J., Barretina, J., Boehm, J. S., Dobson, J., Urashima, M., et al. (2010) · Nature · doi:10.1038/nature08822 · Cited by 4,017 · see citing works
Comprehensive genomic characterization of squamous cell lung cancers
The Cancer Genome Atlas Research Network (2012) · Nature · doi:10.1038/nature11404 · Cited by 3,994 · see citing works
Pao, W., Miller, V. A., Politi, K. A., Riely, G. J., Somwar, R., Zakowski, M. F., Kris, M. G., & Varmus, H. (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0020073 · Cited by 3,527 · see citing works
Genotypic and Histological Evolution of Lung Cancers Acquiring Resistance to EGFR Inhibitors
Sequist, L. V., Waltman, B. A., Dias-Santagata, D., Digumarthy, S., Turke, A. B., Fidias, P., Bergethon, K., Shaw, A. T., Gettinger, S., Cosper, A. K., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002003 · Cited by 3,499 · see citing works
Crizotinib versus Chemotherapy in Advanced <i>ALK</i> -Positive Lung Cancer
Shaw, A. T., Kim, D.-W., Nakagawa, K., Seto, T., Crinó, L., Ahn, M.-J., De Pas, T., Besse, B., Solomon, B. J., Blackhall, F., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1214886 · Cited by 3,381 · cited 1× · see citing works
“A large phase 3 trial has demonstrated the superiority to standard chemotherapy in patients with previously treated advanced NSCLC with ALK rearrangement [80].”
BackgroundSequist, L. V., Yang, J. C.-H., Yamamoto, N., O'Byrne, K., Hirsh, V., Mok, T., Geater, S. L., Orlov, S., Tsai, C.-M., Boyer, M., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.44.2806 · Cited by 3,228 · cited 20× · see citing works
“Data from several clinical trials have indicated that patients with EGFR mutations have improved progression-free survival (PFS) and overall survival (OS) when treated with EGFR inhibitors compared to patients with the same mutations who received standard-of-care, cytotoxic chemotherapy regimens [13-15].”
MethodInfluentialWolchok, J. D., Hoos, A., O'Day, S. J., Weber, J. S., Hamid, O., Lebbé, C., Maio, M., Binder, M., Bohnsack, O., Nichol, G. M., et al. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-1624 · Cited by 3,214 · cited 1× · see citing works
“Therefore, assessment of responses to immune therapy is being reconsidered [235].”
BackgroundEpidermal growth factor receptor mutations in lung cancer
Sharma, S. V., Bell, D. W., Settleman, J., & Haber, D. A. (2007) · Nature Reviews Cancer · doi:10.1038/nrc2088 · Cited by 3,170 · cited 1× · see citing works
“Overexpression of EGFR occurs in up to 60% of NSCLC, with higher frequency in AC versus SQCC (reviewed in [9, 10]).”
BackgroundBrahmer, J. R., Drake, C. G., WOLLNER, I. S., Powderly, J. D., Picus, J., Sharfman, W. H., Stankevich, E., Pons, A., Salay, T. M., McMiller, T. L., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.26.7609 · Cited by 2,967 · cited 1× · see citing works
“A phase 1 trial showed limited responses in patients with different malignancies, including mixed responses in one enrolled NSCLC patient [243].”
BackgroundBET Bromodomain Inhibition as a Therapeutic Strategy to Target c-Myc
Delmore, J. E., Issa, G. C., Lemieux, M. E., Rahl, P. B., Shi, J., Jacobs, H. M., Kastritis, E., Gilpatrick, T., Paranal, R. M., Qi, J., et al. (2011) · Cell · doi:10.1016/j.cell.2011.08.017 · Cited by 2,820 · cited 1× · see citing works
“Transcriptional activity of MYC might be one of the converging factors of the activation of MAPK and PI3K pathways, and it could be targeted at the level of MYC accessory transcription factors such as bromodomaincontaining proteins [185].”
BackgroundSomatic mutations affect key pathways in lung adenocarcinoma
Ding, L., Getz, G., Wheeler, D. A., Mardis, E. R., McLellan, M. D., Cibulskis, K., Sougnez, C., Greulich, H., Muzny, D. M., Morgan, M. B., et al. (2008) · Nature · doi:10.1038/nature07423 · Cited by 2,681 · cited 2× · see citing works
“MET mutations have been observed in about 5% of treatment-naive NSCLC [88], mainly within exons 2 and 14, outside of the kinase domain.”
BackgroundK-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions
Ostrem, J. M., Peters, U., Sos, M. L., Wells, J. A., & Shokat, K. M. (2013) · Nature · doi:10.1038/nature12796 · Cited by 2,557 · cited 1× · see citing works
“Lastly, the “untargetability” of KRAS has been challenged recently, with development of specific smallmolecule inhibitors against KRAS (G12C) that have undergone preclinical testing, and hopefully will come to clinical fruition [149].”
BackgroundGlobal Survey of Phosphotyrosine Signaling Identifies Oncogenic Kinases in Lung Cancer
Rikova, K., Guo, A., Zeng, Q., Possemato, A., Yu, J., Haack, H., Nardone, J., Lee, K., Reeves, C., Li, Y., et al. (2007) · Cell · doi:10.1016/j.cell.2007.11.025 · Cited by 2,317 · cited 1× · see citing works
“The fusions of ROS with SLC34A2 and CD74 were identified in a phosphoproteomic screen of tyrosine kinase activity in lung cancer [115], and have been observed predominantly in AC [116, 117].”
BackgroundKobayashi, A., Kang, M.-I., Okawa, H., Ohtsuji, M., Zenke, Y., Chiba, T., Igarashi, K., & Yamamoto, M. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.16.7130-7139.2004 · Cited by 2,224 · cited 11× · see citing works
“Kelch-like ECH-associated protein 1 (KEAP1) is a ubiquitin ligase that negatively regulates NRF2 activity by targeting it for proteasomal degradation.”
BackgroundInfluentialThe T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP
Yun, C.-H., Mengwasser, K. E., Toms, A. V., Woo, M. S., Greulich, H., Wong, K.-K., Meyerson, M., & Eck, M. J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709662105 · Cited by 2,118 · cited 1× · see citing works
“The T790M mutation affects the gatekeeper residue in the catalytic-kinase domain and confers drug resistance by increasing EGFR’s affinity for ATP – thus reducing the potency of the ATP-competitive kinase inhibitors [39].”
BackgroundIrradiation and anti–PD-L1 treatment synergistically promote antitumor immunity in mice
Deng, L., Liang, H. L., Burnette, B., Beckett, M., Darga, T. E., Weichselbaum, R. R., & Fu, Y. (2014) · Journal of Clinical Investigation · doi:10.1172/jci67313 · Cited by 2,101 · cited 1× · see citing works
“A recent study conducted in animal model (breast cancer) suggested that irradiation leads to elevated expression of PD-L1 in tumors and increases the efficacy of anti-PD-L1 treatments [237].”
BackgroundClinical Features and Outcome of Patients With Non–Small-Cell Lung Cancer Who Harbor EML4-ALK
Shaw, A. T., Yeap, B. Y., Mino-Kenudson, M. A., Digumarthy, S. R., Costa, D. B., Heist, R. S., Solomon, B., Stubbs, H., Admane, S., McDermott, U., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.22.6993 · Cited by 1,873 · cited 1× · see citing works
“EML4-ALK fusions are found in about 3% to13 % of NSCLC patients [76], and are largely mutually exclusive”
BackgroundMapping the Hallmarks of Lung Adenocarcinoma with Massively Parallel Sequencing
Imielinski, M., Berger, A. H., Hammerman, P. S., Hernandez, B., Pugh, T. J., Hodis, E., Cho, J., Suh, J., Capelletti, M., Sivachenko, A., et al. (2012) · Cell · doi:10.1016/j.cell.2012.08.029 · Cited by 1,789 · cited 10× · see citing works
“ACs often contain loss-of-function mutations in other tumor suppressor genes – the most prominent, in addition to TP53, being loss of function of LKB1/STK11, NF1, CDKN2A, SMARCA4, and KEAP1.”
BackgroundInfluentialBean, J., Brennan, C., Shih, J.-Y., Riely, G., Viale, A., Wang, L., Chitale, D., Motoi, N., Szoke, J., Broderick, S., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0710370104 · Cited by 1,598 · cited 1× · see citing works
“MET amplification, as mentioned above, is one of the mechanisms of the acquired resistance to EGFR inhibitors and occurs in about 20% of treated patients [90], but only in 1.”
BackgroundIntegrative genome analyses identify key somatic driver mutations of small-cell lung cancer
Peifer, M., Fernandez‐Cuesta, L., Sos, M. L., George, J., Seidel, D., Kasper, L. H., Plenker, D., Leenders, F., Sun, R., Zander, T., et al. (2012) · Nature Genetics · doi:10.1038/ng.2396 · Cited by 1,390 · cited 5× · see citing works
“FGFR1 is the only RTK amplified at appreciable frequency (6%) in SCLC [5].”
BackgroundInfluentialRET, ROS1 and ALK fusions in lung cancer
Takeuchi, K., Soda, M., Togashi, Y., Suzuki, R., Sakata, S., Hatano, S., Asaka, R., Hamanaka, W., Ninomiya, H., Uehara, H., et al. (2012) · Nature Medicine · doi:10.1038/nm.2658 · Cited by 1,320 · cited 6× · see citing works
“ROS1 rearrangement defines a molecular subset of NSCLC with clinical characteristics that are similar to those observed in patients with ALKrearranged or EGFR-mutated NSCLC [117].”
BackgroundInfluentialActivation of the PD-1 Pathway Contributes to Immune Escape in EGFR-Driven Lung Tumors
Akbay, E. A., Koyama, S., Carretero, J., Altabef, A. B., Tchaicha, J. H., Christensen, C. L., Mikse, O. R., Cherniack, A. D., Beauchamp, E. M., Pugh, T. J., et al. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0310 · Cited by 1,237 · see citing works
Cappuzzo, F., Ciuleanu, T., Stelmakh, L., Cicenas, S., Szczésna, A., Juhász, E., Esteban, E., Molinier, O., Brugger, W., Melezínek, I., et al. (2010) · The Lancet Oncology · doi:10.1016/s1470-2045(10)70112-1 · Cited by 1,186 · see citing works
Genomic Landscape of Non-Small Cell Lung Cancer in Smokers and Never-Smokers
Govindan, R., Ding, L., Griffith, M., Subramanian, J., Dees, N. D., Kanchi, K., Maher, C. A., Fulton, R. S., Fulton, L., Wallis, J. W., et al. (2012) · Cell · doi:10.1016/j.cell.2012.08.024 · Cited by 1,144 · see citing works
Hofstra, R. M. W., Landsvater, R. M., Ceccherini, I., Stulp, R. P., Stelwagen, T., Luo, Y., Pasini, B., Höppener, J. W. M., van Amstel, H. K. P., Romeo, G., et al. (1994) · Nature · doi:10.1038/367375a0 · Cited by 1,143 · cited 1× · see citing works
“RET rearrangements are common (30%) in papillary thyroid carcinomas [120], and mutations are found in 50% of medullary thyroid carcinomas [121].”
BackgroundCharacterizing the cancer genome in lung adenocarcinoma
Weir, B. A., Woo, M. S., Getz, G., Perner, S., Ding, L., Beroukhim, R., Lin, W. M., Province, M. A., Kraja, A., Johnson, L. A., et al. (2007) · Nature · doi:10.1038/nature06358 · Cited by 1,105 · cited 1× · see citing works
“1 is amplified in up to 20% of lung adenocarcinoma, but not in SQCC [4, 200, 201].”
BackgroundHedgehog signalling within airway epithelial progenitors and in small-cell lung cancer
Watkins, D. N., Berman, D. M., Burkholder, S. G., Wang, B., Beachy, P. A., & Baylin, S. B. (2003) · Nature · doi:10.1038/nature01493 · Cited by 1,082 · cited 1× · see citing works
“Hedgehog (HH) pathway is frequently activated in SCLC [224] as seen in the immunochemistry analysis of tumors [225].”
BackgroundLKB1 modulates lung cancer differentiation and metastasis
Ji, H., Ramsey, M. R., Hayes, D. N., Fan, C., McNamara, K., Kozlowski, P., Torrice, C., Wu, M. C., Shimamura, T., Perera, S. A., et al. (2007) · Nature · doi:10.1038/nature06030 · Cited by 1,064 · cited 2× · see citing works
“Another study found inactivation of LKB1 in 34% and 19% of 144 human lungs in AC and SQCC, respectively [169].”
BackgroundDoebele, R. C., Pilling, A. B., Aisner, D. L., Kutateladze, T. G., Le, A. T., Weickhardt, A. J., Kondo, K. L., Linderman, D. J., Heasley, L. E., Franklin, W. A., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-2906 · Cited by 1,064 · cited 1× · see citing works
“Another study of resistance to crizotinib also identified secondary mutations in ALK, in EGFR, and in KRAS [84].”
BackgroundDysfunctional KEAP1–NRF2 Interaction in Non-Small-Cell Lung Cancer
Singh, A., Misra, V., Thimmulappa, R. K., Lee, H., Ames, S., Hoque, M. O., Herman, J. G., Baylin, S. B., Sidransky, D., Gabrielson, E., et al. (2006) · PLoS Medicine · doi:10.1371/journal.pmed.0030420 · Cited by 1,060 · cited 1× · see citing works
“Inactivation of KEAP1 is a frequent event in NSCLC [194], with mutations and copynumber losses in ~11% of AC and 12% of SQCC cases.”
BackgroundByers, L. A., Diao, L., Wang, J., Saintigny, P., Girard, L., Peyton, M., Shen, L., Fan, Y., Giri, U., Tumula, P. K., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-1558 · Cited by 1,059 · cited 1× · see citing works
“AXL drives a mesenchymal phenotype, and resulting tumors acquire sensitivity to AXL inhibitor SGI-7079 [44].”
BackgroundPreexistence and clonal selection of MET amplification in EGFR mutant NSCLC
Turke, A. B., Zejnullahu, K., Wu, Y.-L., Song, Y., Dias-Santagata, D., Lifshits, E., Toschi, L., Rogers, A., Mok, T., Sequist, L., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2009.11.022 · Cited by 1,059 · see citing works
The quest to overcome resistance to EGFR-targeted therapies in cancer
Chong, C. R., & Janne, P. A. (2013) · Nature Medicine · doi:10.1038/nm.3388 · Cited by 1,055 · cited 1× · see citing works
“Several mechanisms have been implicated in resistance to EGFR inhibitors, and they were reviewed recently [35-37].”
BackgroundBRAF and RAS mutations in human lung cancer and melanoma.
Brose, M. S., Volpe, P., Feldman, M. D., Kumar, M. S., Rishi, I., Gerrero, R. M., Einhorn, E., Herlyn, M., Minna, J. D., Nicholson, A. G., et al. (2002) · PubMed · Cited by 1,053 · see citing works
Lynch, T. J., Bondarenko, I., Luft, A. V., Serwatowski, P., Barlési, F., Chacko, R. T., Sebastian, M., Neal, J. W., Lu, H., Cuillerot, J.-M., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2011.38.4032 · Cited by 999 · see citing works
Gazdar, A. F. (2009) · Oncogene · doi:10.1038/onc.2009.198 · Cited by 991 · cited 1× · see citing works
“Eighty-five percent of all EGFR-activating mutations are exon 19 in-frame deletions or L858R, and they tend to be sensitive to currently approved EGFR inhibitors (reviewed in [11]).”
BackgroundSOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas
Bass, A. J., Watanabe, H., Mermel, C. H., Yu, S., Perner, S., Verhaak, R. G. W., Kim, S. Y., Wardwell, L., Tamayo, P., Gat‐Viks, I., et al. (2009) · Nature Genetics · doi:10.1038/ng.465 · Cited by 941 · cited 1× · see citing works
“SOX2 amplification was detected in SQCC of lung and esophagus, and is required for survival of SQCC cell lines [209]; an NGS study [4] identified SOX2 amplification in 21% of lung SQCC.”
BackgroundKIF5B-RET fusions in lung adenocarcinoma
Kohno, T., Ichikawa, H., Totoki, Y., Yasuda, K., Hiramoto, M., Nammo, T., Sakamoto, H., Tsuta, K., Furuta, K., Shimada, Y., et al. (2012) · Nature Medicine · doi:10.1038/nm.2644 · Cited by 834 · cited 1× · see citing works
“The most common fusion partner of RET in NSCLC is KIF5B, a gene in the family of motor proteins, kinesins [117, 123, 124].”
BackgroundWeiss, J. M., Sos, M. L., Seidel, D., Peifer, M., Zander, T., Heuckmann, J. M., Ullrich, R. T., Menon, R., Maier, S. H., Soltermann, A., et al. (2010) · Science Translational Medicine · doi:10.1126/scitranslmed.3001451 · Cited by 833 · see citing works
Intragenic ERBB2 kinase mutations in tumours
Stephens, P., Hunter, C., Bignell, G., Edkins, S., Davies, H., Teague, J., Stevens, C., O'Meara, S., Smith, R., Parker, A., et al. (2004) · Nature · doi:10.1038/431525b · Cited by 802 · cited 1× · see citing works
“Mutations in HER2 were identified in 2% to 4% of NSCLC examined [99-101].”
BackgroundJackman, D., Pao, W., Riely, G. J., Engelman, J. A., Kris, M. G., Jänne, P. A., Lynch, T., Johnson, B. E., & Miller, V. A. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.24.7049 · Cited by 793 · cited 1× · see citing works
“However, nearly all patients with EGFR-mutantAC develop resistance to the first-generation inhibitors erlotinib and gefitinib, with a median PFS of 14 months [34].”
BackgroundLinardou, H., Dahabreh, I. J., Kanaloupiti, D., Siannis, F., Bafaloukos, D., Kosmidis, P., Papadimitriou, C. A., & Murray, S. (2008) · The Lancet Oncology · doi:10.1016/s1470-2045(08)70206-7 · Cited by 739 · see citing works
Takezawa, K., Pirazzoli, V., Arcila, M. E., Nebhan, C. A., Song, X., de Stanchina, E., Ohashi, K., Janjigian, Y. Y., Spitzler, P. J., Melnick, M. A., et al. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0108 · Cited by 710 · cited 2× · see citing works
“Another mechanism of resistance is amplification of HER2 reported to occur in 12% of tumors that developed resistance to EGFR inhibitors [47].”
BackgroundClinical Characteristics of Patients With Lung Adenocarcinomas Harboring BRAF Mutations
Paik, P. K., Arcila, M. E., Fara, M. G., Sima, C. S., Miller, V. A., Kris, M. G., Ladanyi, M., & Riely, G. J. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.33.1280 · Cited by 692 · cited 2× · see citing works
“BRAF mutations occur much more commonly in smokers than in nonsmokers [156].”
BackgroundSomatic Mutations of the <i>HER2</i> Kinase Domain in Lung Adenocarcinomas
Shigematsu, H., Takahashi, T., Nomura, M., Majmudar, K., Suzuki, M., Lee, H., Wistuba, I. I., Fong, K. M., Toyooka, S., Shimizu, N., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-4235 · Cited by 678 · cited 1× · see citing works
“Mutations in HER2 were identified in 2% to 4% of NSCLC examined [99-101].”
BackgroundOncogenic Transformation by Inhibitor-Sensitive and -Resistant EGFR Mutants
Greulich, H., Chen, T.-H., Feng, W., Jänne, P. A., Alvarez, J. V., Zappaterra, M., Bulmer, S. E., Frank, D. A., Hahn, W. C., Sellers, W. R., et al. (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0020313 · Cited by 677 · see citing works
Mazières, J., Peters, S., Lepage, B., Cortot, A. B., Barlesi, F., Beau-Faller, M., Besse, B., Blons, H., Mansuet-Lupo, A., Urban, T., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.45.6095 · Cited by 668 · cited 3× · see citing works
“Responses were observed with trastuzumab and afatinib [102, 107] but not with other EGFR-family-targeted drugs such as gefitinib or lapatinib [108, 109].”
BackgroundResultActivation of ERBB2 signaling causes resistance to the EGFR-directed therapeutic antibody cetuximab
Yonesaka, K., Zejnullahu, K., Okamoto, I., Satoh, T., Cappuzzo, F., Souglakos, J., Ercan, D., Rogers, A., Roncalli, M., Takeda, M., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002442 · Cited by 663 · see citing works
Jänne, P. A., Shaw, A. T., Pereira, J. R., Jeannin, G., Vansteenkiste, J., Barrios, C., Franke, F. A., Grinsted, L., Zazulina, V., Smith, P., et al. (2013) · The Lancet Oncology · doi:10.1016/s1470-2045(12)70489-8 · Cited by 655 · see citing works
Wnt Signaling Pathway in Non-Small Cell Lung Cancer
Stewart, D. J. (2013) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djt356 · Cited by 653 · cited 1× · see citing works
“Still, there is evidence that inhibition of WNT pathway in vitro inhibits proliferation of lung cancer cells and downregulation of WNT-pathway inhibitory proteins in cell lines and tumor biopsies (reviewed in [205]).”
BackgroundOxnard, G. R., Arcila, M. E., Sima, C. S., Riely, G. J., Chmielecki, J., Kris, M. G., Pao, W., Ladanyi, M., & Miller, V. A. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-2692 · Cited by 627 · see citing works
Inactivation of LKB1/STK11 is a common event in adenocarcinomas of the lung.
Sánchez‐Céspedes, M., Parrella, P., Esteller, M., Nomoto, S., Trink, B., Engles, J. M., Westra, W. H., Herman, J. G., & Sidransky, D. (2002) · PubMed · Cited by 626 · see citing works
Walter, A. O., Sjin, R. T. T., Haringsma, H. J., Ohashi, K., Sun, J., Lee, K., Dubrovskiy, A., Labenski, M., Zhu, Z., Wang, Z., et al. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0314 · Cited by 620 · cited 16× · see citing works
“A recent study has found that a low level of PTEN expression does not necessarily signify high activity of AKT, and that areas with different levels of AKT activation co-exist within the same adenocarcinoma of lung [165].”
BackgroundInfluentialOncogenic and drug-sensitive NTRK1 rearrangements in lung cancer
Vaishnavi, A., Capelletti, M., Le, A. T., Kako, S. L., Butaney, M., Ercan, D., Mahale, S., Davies, K. D., Aisner, D. L., Pilling, A. B., et al. (2013) · Nature Medicine · doi:10.1038/nm.3352 · Cited by 615 · see citing works
Gainor, J. F., Varghese, A. M., Ou, S. I., Kabraji, S. K., Awad, M. M., Katayama, R., Pawlak, A. C., Mino-Kenudson, M. A., Yeap, B. Y., Riely, G. J., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-0318 · Cited by 609 · see citing works
Mascaux, C., Iannino, N., Martin, B., Paesmans, M., Berghmans, T., Dusart, M., Haller, A., Lothaire, P., Meert, A.-P., Noël, S., et al. (2004) · British Journal of Cancer · doi:10.1038/sj.bjc.6602258 · Cited by 604 · cited 1× · see citing works
“In clinical trials, the prognostic significance of KRAS mutations in NSCLC has been variable, with some trials and pooled analyses reporting worse overall prognosis and others failing to identify any difference in survival outcomes [142, 143].”
ResultSmall molecule inhibition of the KRAS–PDEδ interaction impairs oncogenic KRAS signalling
Zimmermann, G., Papke, B., Ismail, S., Vartak, N., Chandra, A., Hoffmann, M., Hahn, S. A., Triola, G., Wittinghofer, A., Bastiaens, P. I. H., et al. (2013) · Nature · doi:10.1038/nature12205 · Cited by 596 · see citing works
DNA Methylation Markers and Early Recurrence in Stage I Lung Cancer
Brock, M. V., Hooker, C. M., Ota-Machida, E., Han, Y. K., Guo, M., Ames, S., Glöckner, S. C., Piantadosi, S., Gabrielson, E. W., Pridham, G., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0706550 · Cited by 594 · cited 1× · see citing works
“The importance of DNA methylation, for example, was recognized when a study demonstrated clinical utility for prognostic purposes of the methylation status of a four-gene panel in early-stage NSCLC [188].”
BackgroundThe Histone Mark H3K36me3 Regulates Human DNA Mismatch Repair through Its Interaction with MutSα
Li, F., Mao, G., Tong, D., Huang, J., Gu, L., Yang, W., & Li, G. (2013) · Cell · doi:10.1016/j.cell.2013.03.025 · Cited by 591 · see citing works
Rousseaux, S., Debernardi, A., Jacquiau, B., Vitte, A.-L., Vesin, A., Nagy-Mignotte, H., Moro‐Sibilot, D., Brichon, P., Lantuéjoul, S., Hainaut, P. L., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3005723 · Cited by 587 · cited 1× · see citing works
“The common molecular features were the acquisition of embryonic stem cell/germ cell gene expression profiles and the down-regulation of immune response genes [199].”
BackgroundShackelford, D. B., Abt, E., Gerken, L., Vasquez, D. S., Seki, A., Leblanc, M., Wei, L., Fishbein, M. C., Czernin, J., Mischel, P. S., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2012.12.008 · Cited by 585 · cited 1× · see citing works
“Biguanide compounds traditionally used for treatment of diabetes have shown activity in pre-clinical models of NSCLC with LKB1 and KRAS mutations [173].”
BackgroundMa, P. C., Jagadeeswaran, R., Jagadeesh, S., Tretiakova, M., Nallasura, V., Fox, E. A., Hansen, M., SCHAEFER, E. M., Naoki, K., Lader, A. S., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-2650 · Cited by 576 · cited 1× · see citing works
“MET overexpression has been observed in 25% to 61% of NSCLC patients [92, 93].”
BackgroundSelf-citationSeto, T., Kiura, K., Nishio, M., Nakagawa, K., Maemondo, M., Inoue, A., Hida, T., Yamamoto, N., Yoshioka, H., Harada, M., et al. (2013) · The Lancet Oncology · doi:10.1016/s1470-2045(13)70142-6 · Cited by 575 · see citing works
Ray-Coquard, I., Blay, J.-Y., Italiano, A., Le Cesne, A., Penel, N., Zhi, J., Heil, F., Rueger, R., Graves, B., Ding, M., et al. (2012) · The Lancet Oncology · doi:10.1016/s1470-2045(12)70474-6 · Cited by 571 · see citing works
Yasuda, H., Park, E., Yun, C.-H., Sng, N. J., Lucena-Araujo, A. R., Yeo, W.-L., Huberman, M. S., Cohen, D. W., Nakayama, S., Ishioka, K., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3007205 · Cited by 571 · see citing works
Byers, L. A., Wang, J., Nilsson, M. B., Fujimoto, J., Saintigny, P., Yordy, J. S., Giri, U. P., Peyton, M., Fan, Y. H., Diao, L., et al. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0112 · Cited by 553 · see citing works
RET Fusions Define a Unique Molecular and Clinicopathologic Subtype of Non–Small-Cell Lung Cancer
Wang, R., Hu, H., Pan, Y., Li, Y., Ye, T., Li, C., Luo, X., Wang, L., Li, H., Zhang, Y., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2012.44.1477 · Cited by 549 · cited 2× · see citing works
“Patients with RET translocations tend to be younger nonsmokers and have poorly differentiated tumors [125].”
BackgroundKatayama, R., Khan, T. M., Benes, C. H., Lifshits, E., Ebi, H., Rivera, V. M., Shakespeare, W. C., Iafrate, A. J., Engelman, J. A., & Shaw, A. T. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1019559108 · Cited by 546 · cited 1× · see citing works
“Although crizotinib was ineffectual against EML4-ALK harboring the gatekeeper mutation, two structurally different ALK inhibitors, NVP-TAE684 and AP26113, were highly active against the resistant cancer cells in vitro and in vivo [85].”
BackgroundWei, Y., Zou, Z., Becker, N., Anderson, M., Sumpter, R., Xiao, G., Kinch, L. N., Koduru, P. R. K., Christudass, C. S., Veltri, R. W., et al. (2013) · Cell · doi:10.1016/j.cell.2013.08.015 · Cited by 531 · see citing works
Vonderheide, R. H., Flaherty, K. T., Khalil, M., Stumacher, M., Bajor, D. L., Hutnick, N. A., Sullivan, P., Mahany, J. J., Gallagher, M., Kramer, A., et al. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2006.08.3311 · Cited by 513 · cited 1× · see citing works
“A large number of cancer patients received infusions of agonistic antibody CP870,893 and some responses were observed [247].”
BackgroundA Genomics-Based Classification of Human Lung Tumors
Thomas, R. K., Buettner, R., & Wolf, J. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3006802 · Cited by 508 · see citing works
Lee, C. K., Brown, C. S. B., Gralla, R. J., Hirsh, V., Thongprasert, S., Tsai, C., Tan, E. H., Ho, J., Chu, D., Zaatar, A., et al. (2013) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djt072 · Cited by 505 · see citing works
Inoue, A., Kobayashi, K., Usui, K., Maemondo, M., Okinaga, S., Mikami, I., Ando, M., Yamazaki, K., Saijo, Y., Gemma, A., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.18.7658 · Cited by 505 · cited 1× · see citing works
“Data from several clinical trials have indicated that patients with EGFR mutations have improved progression-free survival (PFS) and overall survival (OS) when treated with EGFR inhibitors compared to patients with the same mutations who received standard-of-care, cytotoxic chemotherapy regimens [13-15].”
BackgroundJu, Y. S., Lee, W., Shin, J.-Y., Lee, S., Bleazard, T., Won, J., Kim, Y. T., Kim, J., Kang, J. H., & Seo, J. (2011) · Genome Research · doi:10.1101/gr.133645.111 · Cited by 486 · cited 1× · see citing works
“The most common fusion partner of RET in NSCLC is KIF5B, a gene in the family of motor proteins, kinesins [117, 123, 124].”
BackgroundMutations in the DDR2 Kinase Gene Identify a Novel Therapeutic Target in Squamous Cell Lung Cancer
Hammerman, P. S., Sos, M. L., Ramos, A. H., Xu, C., Dutt, A., Zhou, W., Brace, L. E., Woods, B. A., Lin, W., Zhang, J., et al. (2011) · Cancer Discovery · doi:10.1158/2159-8274.cd-11-0005 · Cited by 480 · cited 2× · see citing works
“8%) SQCC samples, may alter kinase activity, ligand binding, or DDR2 localization [132].”
BackgroundSpigel, D. R., Ervin, T. J., Ramlau, R., Daniel, D. B., Goldschmidt, J. H., Blumenschein, G. R., Krzakowski, M. J., Robinet, G., Godbert, B., Barlési, F., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.47.4189 · Cited by 479 · cited 1× · see citing works
“However, the phase III trial of Onartuzumab combined with erlotinib in MET positive EGFR mutant NSCLC failed to improve PFS or OS in spite of the positive results from a phase II trial [59].”
ResultRET tyrosine kinase signaling in development and cancer.
Arighi, E., Borrello, M. G., & Sariola, H. (2005) · Cytokine & growth factor reviews · doi:10.1016/j.cytogfr.2005.05.010 · Cited by 476 · cited 1× · see citing works
“RET ligands belong to the glial cell-derived neurotrophic (GDNF) family, and upon engagement, RET induces activation of multiple signaling pathways: PI3K, MAPK, JNK, p38, SRC, ERK5, PLC-γ, and STAT [122].”
BackgroundGarassino, M. C., Martelli, O., Broggini, M., Farina, G., Veronese, S., Rulli, E., Bianchi, F., Bettini, A., Longo, F., Moscetti, L., et al. (2013) · The Lancet Oncology · doi:10.1016/s1470-2045(13)70310-3 · Cited by 475 · see citing works
Response to Cabozantinib in Patients with RET Fusion-Positive Lung Adenocarcinomas
Drilon, A. E. D. C., Wang, L., Hasanovic, A., Suehara, Y., Lipson, D., Stephens, P. J., Ross, J. S., Miller, V. A., Ginsberg, M. S., Zakowski, M. F., et al. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0035 · Cited by 467 · cited 1× · see citing works
“Significant increases in PFS were reported in three out of three patients with RETrearranged AC in a small trial of cabozantinib [126].”
BackgroundAIS is an oncogene amplified in squamous cell carcinoma
Hibi, K., Trink, B., Patturajan, M., Westra, W. H., Caballero, O. L., Hill, D. E., Ratovitski, E. A., Jen, J., & Sidransky, D. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.10.5462 · Cited by 464 · cited 1× · see citing works
“Amplification of TP63 was reported in SQCC-derived cell lines [218] and in 16% of tumors [4].”
BackgroundNotch-Dependent Differentiation of Adult Airway Basal Stem Cells
Rock, J. R., Gao, X., Xue, Y., Randell, S. H., Kong, Y., & Hogan, B. L. M. (2011) · Cell stem cell · doi:10.1016/j.stem.2011.04.003 · Cited by 459 · cited 1× · see citing works
“However, in progenitor basal cells of airway epithelium Notch signaling is required for differentiation but not cell renewal [214], perhaps explaining the role of abrogated Notch signaling in pathogenesis of lung SQCC.”
BackgroundAn achaete-scute homologue essential for neuroendocrine differentiation in the lung
Borges, M. W., Linnoila, R. I., van de Velde, H. J. K., Chen, H., Nelkin, B. D., Mabry, M. H., Baylin, S. B., & Ball, D. W. (1997) · Nature · doi:10.1038/386852a0 · Cited by 455 · cited 1× · see citing works
“ASCL1 is a lineage-specific, basic helix-loop-helix member of the achaete-scute family, and it is essential for differentiation of numerous pulmonary neuroendocrine (NE) cells and tissues during lung development [220].”
BackgroundOhashi, K., Sequist, L. V., Arcila, M. E., Moran, T., Chmielecki, J., Lin, Y.-L., Pan, Y., Wang, L., de Stanchina, E., Shien, K., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1203530109 · Cited by 441 · cited 1× · see citing works
“An extensive study examined potential involvement of mutations in BRAF, NRAS, KRAS, and MEK1 in a large number of resistant tumors, and found no evidence of secondary mutations in these genes with the exception of BRAF, where mutations were identified in 2 of 195 (1%) biopsies [48].”
BackgroundPredictive Gene Signature in MAGE-A3 Antigen-Specific Cancer Immunotherapy
Ulloa-Montoya, F., Louahed, J., Dizier, B., Gruselle, O., Spiessens, B., Lehmann, F. F., Suciu, S., Kruit, W. H. J., Eggermont, A. M. M., Vansteenkiste, J., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.44.3762 · Cited by 436 · cited 1× · see citing works
“This suggests that the tumor’s immune microenvironment plays a major role in the patient’s clinical response [251].”
BackgroundStrohecker, A. M., Guo, J. Y., Karsli-Uzunbas, G., Price, S. M., Chen, G. J., Mathew, R., McMahon, M., & White, E. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0397 · Cited by 435 · see citing works
Notch signaling induces cell cycle arrest in small cell lung cancer cells.
Sriuranpong, V., Borges, M. W., Ravi, R. K., Arnold, D. R., Nelkin, B. D., Baylin, S. B., & Ball, D. W. (2001) · PubMed · Cited by 435 · see citing works
Solis, L. M., Behrens, C., Dong, W., Suraokar, M. B., Ozburn, N. C., Moran, C. A., Corvalán, A. H., Biswal, S. S., Swisher, S. G., Bekele, B. N., et al. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-3352 · Cited by 430 · cited 1× · see citing works
“Nuclear localization of NRF2 (assumed by NRF2 protein that is not bound by KEAP1) was seen in 26% of NSCLCs; it was significantly more common in SQCCs (38%) than in adenocarcinomas (18%), and is associated with poor prognosis [196].”
BackgroundPIK3CA Mutations and Copy Number Gains in Human Lung Cancers
Yamamoto, H., Shigematsu, H., Nomura, M., Lockwood, W. W., Sato, M., Okumura, N., Soh, J., Suzuki, M., Wistuba, I. I., Fong, K. M., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-5084 · Cited by 429 · cited 1× · see citing works
“6% of AC [161], with exon 9 as the most frequently mutated site.”
BackgroundShi, Y., Zhang, L., Liu, X., Zhou, C., Zhang, L., Zhang, S., Wang, D., Li, Q., Qin, S., Hu, C., et al. (2013) · The Lancet Oncology · doi:10.1016/s1470-2045(13)70355-3 · Cited by 422 · see citing works
Acquired Resistance to Crizotinib from a Mutation in CD74 – ROS1
Awad, M. M., Katayama, R., McTigue, M. A., Liu, W., Deng, Y.-L., Brooun, A., Friboulet, L., Huang, D., Falk, M. D., Timofeevski, S. L., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1215530 · Cited by 421 · see citing works
A new oncogene in human thyroid papillary carcinomas and their lymph-nodal metastases
Fusco, A., Grieco, M., Santoro, M. M., Berlingieri, M. T., Pilotti, S., Pierotti, M. A., Porta, G., & Vecchio, G. (1987) · Nature · doi:10.1038/328170a0 · Cited by 412 · cited 1× · see citing works
“RET rearrangements are common (30%) in papillary thyroid carcinomas [120], and mutations are found in 50% of medullary thyroid carcinomas [121].”
BackgroundYang, J. C., Shih, J., Su, W., Hsia, T., Tsai, C., Ou, S. I., Yu, C., Chang, G., Ho, C., Sequist, L. V. D., et al. (2012) · The Lancet Oncology · doi:10.1016/s1470-2045(12)70086-4 · Cited by 410 · see citing works
Lehmann, S., Bykov, V. J. N., Ali, D., Andrén, O., Cherif, H., Tidefelt, U., Uggla, B., Yachnin, J., Juliusson, G., Moshfegh, A., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2011.40.7783 · Cited by 406 · see citing works
Gatzemeier, U., Groth, G., Butts, C. A., van Zandwijk, N., Shepherd, F. A., Ardizzoni, A., Barton, C. M., Ghahramani, P., & Hirsh, V. (2003) · Annals of Oncology · doi:10.1093/annonc/mdh031 · Cited by 388 · see citing works
Alterations of immune response of non-small cell lung cancer with Azacytidine
Wrangle, J. M., Wang, W., Koch, A., Easwaran, H., Mohammad, H. P., Pan, X., Vendetti, F. P., Criekinge, W. V., DeMeyer, T., Du, Z., et al. (2013) · Oncotarget · doi:10.18632/oncotarget.1542 · Cited by 385 · cited 1× · see citing works
“The role of demethylating agents in modulating the response to immune-checkpoint inhibition is explored in trial NCT01928576; this involves pretreatment with azacytidine, entinostat, or CC-486 which, according to a recent study might sensitize NSCLC to anti-PD1 therapy [245].”
BackgroundSequist, L. V. D., von Pawel, J., Garmey, E. G., Akerley, W., Brugger, W., Ferrari, D., Chen, Y., Costa, D. B., Gerber, D. E., Орлов, С. В., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.34.0570 · Cited by 380 · see citing works
Corcoran, R. B., Cheng, K. A., Hata, A. N., Faber, A. C., Ebi, H., Coffee, E. M., Greninger, P., Brown, R. D., Godfrey, J. T., Cohoon, T. J., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2012.11.007 · Cited by 377 · cited 1× · see citing works
“com/oncotarget identified BCL-XL and MEK inhibition as a potentially successful strategy for treatment of KRAS-mutant adenocarcinoma [146].”
BackgroundCardarella, S., Ogino, A., Nishino, M., Butaney, M., Shen, J., Lydon, C., Yeap, B. Y., Sholl, L. M., Johnson, B. E., & Janne, P. A. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-0657 · Cited by 375 · cited 1× · see citing works
“Only about half of BRAF mutations in NSCLC are V600E [157].”
BackgroundNotch signaling controls the balance of ciliated and secretory cell fates in developing airways
Tsao, P., Vasconcelos, M., Izvolsky, K. I., Qian, J., Lü, J., & Cardoso, W. V. (2009) · Development · doi:10.1242/dev.034884 · Cited by 374 · cited 1× · see citing works
“Notch signaling is required for the cell- fate decision between ciliated and non-ciliated secretory epithelium in developing lung [213].”
BackgroundMolecular Pathways: ROS1 Fusion Proteins in Cancer
Davies, K. D., & Doebele, R. C. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-2851 · Cited by 373 · see citing works
Binding of GAP to Activated PDGF Receptors
Kazlauskas, A., Ellis, C. A., Pawson, T. J., & Cooper, J. A. (1990) · Science · doi:10.1126/science.2157284 · Cited by 369 · cited 1× · see citing works
“RASA1 (p120Ras GAP) is a well-known GTPaseactivating protein (GAP) that functions as a negative regulator of Ras signaling downstream of several growth-factor receptors [154].”
BackgroundInhibitor-Sensitive FGFR1 Amplification in Human Non-Small Cell Lung Cancer
Dutt, A., Ramos, A. H., Hammerman, P. S., Mermel, C. H., Cho, J., Sharifnia, T., Chande, A. G., Tanaka, K., Stransky, N., Greulich, H. E., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0020351 · Cited by 367 · cited 1× · see citing works
“Focal amplification of FGFR1 was detected in 21% to 22% of SQCC tumors according to two reports [127, 128], but is quite rare in AC (1% to 3%) [2, 128].”
BackgroundNemunaitis, J. J., Dillman, R. O., Schwarzenberger, P. O., Senzer, N. N., Cunningham, C. C., Cutler, J., Tong, A., Kumar, P., Pappen, B. O., Hamilton, C., et al. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2005.05.5335 · Cited by 365 · cited 1× · see citing works
“Lucanix, or Belagenpumatucel-L, a vaccine consisting of allogeneic NSCLC cells transfected with an antisense plasmid to TGFα2 was in clinical trials [253], with promising results, and is now in phase 3 trial NCT00676507.”
BackgroundJahchan, N. S., Dudley, J. T., Mazur, P. K., Flores, N. M., Yang, D., Palmerton, A., Zmoos, A., Vaka, D., Tran, K. Q. T., Zhou, M. J., et al. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0183 · Cited by 358 · see citing works
Yap, T. A., Vidal, L., Adam, J., Stephens, P., Spicer, J., Shaw, H., Ang, J., Temple, G., Bell, S., Shahidi, M., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.26.7278 · Cited by 349 · cited 1× · see citing works
“The secondgeneration TKIs such as afatinib (BIBW2992) described above irreversibly inhibit RTKs of EGFR family, as well as the T790M variant of EGFR [21, 54].”
BackgroundEmerging Paradigms in the Development of Resistance to Tyrosine Kinase Inhibitors in Lung Cancer
Gainor, J. F., & Shaw, A. T. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.45.2029 · Cited by 349 · cited 1× · see citing works
“Several mechanisms have been implicated in resistance to EGFR inhibitors, and they were reviewed recently [35-37].”
BackgroundRegulation of repulsion versus adhesion by different splice forms of an Eph receptor
Holmberg, J., Clarke, D. L., & Frisén, J. (2000) · Nature · doi:10.1038/35041577 · Cited by 335 · cited 1× · see citing works
“EPHA7 plays an important role in development and regulates repulsion versus adhesion of migrating cells, including during neural tube formation [230].”
BackgroundKatakami, N., Atagi, S., Goto, K., Hida, T., Horai, T., Inoue, A., Ichinose, Y., Koboyashi, K., Takeda, K., Kiura, K., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.45.0981 · Cited by 326 · see citing works
Onozato, R., Kosaka, T., Kuwano, H., Sekido, Y., Yatabe, Y., & Mitsudomi, T. (2009) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e3181913e0e · Cited by 326 · cited 2× · see citing works
“4% of treatment-naïve patients [91], exclusively in AC.”
BackgroundClinicopathologic Features of Non-Small-Cell Lung Cancer with EML4–ALK Fusion Gene
Takahashi, T., Sonobe, M., Kobayashi, M., Yoshizawa, A., Menju, T., Nakayama, E., Mino, N., Iwakiri, S., Sato, K., Miyahara, R., et al. (2009) · Annals of Surgical Oncology · doi:10.1245/s10434-009-0808-7 · Cited by 326 · cited 1× · see citing works
“Patients with EML4-ALK mutant tumors are characteristically younger, and like patients with EGFR-mutated NSCLC, they typically are never smokers with AC histology [78].”
BackgroundCTLA-4 is constitutively expressed on tumor cells and can trigger apoptosis upon ligand interaction
Contardi, E., Palmisano, G. L., Tazzari, P. L., Martelli, A. M., Falà, F., Fabbi, M., Kato, T., Lucarelli, E., Donati, D. M., Polito, L., et al. (2005) · International Journal of Cancer · doi:10.1002/ijc.21155 · Cited by 324 · see citing works
Mechanism of MEK inhibition determines efficacy in mutant KRAS- versus BRAF-driven cancers
Hatzivassiliou, G., Haling, J. R., Chen, H., Song, K. W., Price, S., Heald, R. A., Hewitt, J. F. M., Zak, M., Peck, A., Orr, C., et al. (2013) · Nature · doi:10.1038/nature12441 · Cited by 323 · see citing works
Vansteenkiste, J., Zielinski, M., Linder, A., Dahabreh, J., Gonzalez, E. E., Malinowski, W., López-Brea, M., Vanakesa, T., Jassem, J., Kalofonos, H. P., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.43.7103 · Cited by 317 · cited 1× · see citing works
“As is often the case in immunotherapy trials, this strategy has shown few but lasting responders [250].”
BackgroundMao, C., Qiu, L., Liao, R.-Y., Du, F.-B., Ding, H., Yang, W.-C., Li, J., & Chen, Q. (2009) · Lung Cancer · doi:10.1016/j.lungcan.2009.11.020 · Cited by 314 · see citing works
Mitsudomi, T., Hamajima, N., Ogawa, M., & Takahashi, T. (2000) · PubMed · Cited by 307 · see citing works
Critical role of p63 in the development of a normal esophageal and tracheobronchial epithelium
Daniely, Y., Liao, G., Dixon, D., Linnoila, R. I., Lori, A., Randell, S. H., Oren, M., & Jetten, A. M. (2004) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00226.2003 · Cited by 300 · cited 1× · see citing works
“TP63 is considered to be a marker of stem cell compartment in different lineages, and is a regulator of squamous cell differentiation involved in the development of tracheobronchial epithelium [216].”
BackgroundInhibition of Myc family proteins eradicates KRas-driven lung cancer in micePreprint
Soucek, L., Whitfield, J. R., Sodir, N. M., Massó-Vallés, D., Serrano, E., Karnezis, A. N., Swigart, L. B., & Evan, G. I. (2013) · Genes & Development · doi:10.1101/gad.205542.112 · Cited by 299 · see citing works
Wu, Y.-L. L. C., Lee, J. S., Thongprasert, S., Yu, C., Zhang, L., Ladrera, G., Srimuninnimit, V., Sriuranpong, V., Sandoval-Tan, J., Zhu, Y., et al. (2013) · The Lancet Oncology · doi:10.1016/s1470-2045(13)70254-7 · Cited by 298 · cited 1× · see citing works
“Addition of erlotinib significantly prolonged PFS in patients with mutant EGFR [32].”
BackgroundJustilien, V., Walsh, M. P., Ali, S. A., Thompson, E. A., Murray, N. R., & Fields, A. P. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.01.008 · Cited by 296 · see citing works
Gontan, C., Munck, A. B., Vermeij, M., Grosveld, F. G., Tibboel, D., & Rottier, R. J. (2008) · Developmental Biology · doi:10.1016/j.ydbio.2008.02.035 · Cited by 294 · cited 1× · see citing works
“HMG box transcription factor SOX2 is a lineagesurvival oncogene expressed during initiation of branching morphogenesis in lung, but enforced high expression of SOX2 prevents branching and differentiation [208].”
BackgroundMissense mutations of the BRAF gene in human lung adenocarcinoma.
Naoki, K., Chen, T. H., Richards, W. G., Sugarbaker, D. J., & Meyerson, M. M. (2002) · PubMed · Cited by 283 · see citing works
Frequent BRG1/SMARCA4-inactivating mutations in human lung cancer cell lines
Medina, P. P., Romero, O. A., Kohno, T., Montuenga, L. M., Pı́o, R., Yokota, J., & Sánchez‐Céspedes, M. (2008) · Human Mutation · doi:10.1002/humu.20730 · Cited by 273 · see citing works
The Biology of Epidermal Growth Factor Receptor in Lung Cancer
Scagliotti, G. V., Selvaggi, G., Novello, S., & Hirsch, F. R. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-040007 · Cited by 270 · cited 1× · see citing works
“Overexpression of EGFR occurs in up to 60% of NSCLC, with higher frequency in AC versus SQCC (reviewed in [9, 10]).”
BackgroundRamalingam, S. S., Blackhall, F. H., Krzakowski, M. J., Barrios, C. H., Park, K., Bover, I., Heo, D. S., Rosell, R., Talbot, D. C., Frank, R. C., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2011.40.9433 · Cited by 263 · see citing works
Bypass Mechanisms of Resistance to Receptor Tyrosine Kinase Inhibition in Lung Cancer
Niederst, M. J., & Engelman, J. A. (2013) · Science Signaling · doi:10.1126/scisignal.2004652 · Cited by 261 · cited 1× · see citing works
“Several mechanisms have been implicated in resistance to EGFR inhibitors, and they were reviewed recently [35-37].”
BackgroundElucidating Distinct Roles for <i>NF1</i> in Melanomagenesis
Maertens, O., Johnson, B., Hollstein, P., Frederick, D. T., Cooper, Z. A., Messiaen, L., Bronson, R. T., McMahon, M., Granter, S., Flaherty, K., et al. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0313 · Cited by 258 · see citing works
Ware, K. E., Hinz, T. K., Kleczko, E. K., Singleton, K. R., Marek, L. A., Helfrich, B., Cummings, C. T., Graham, D. K., Astling, D. P., Tan, A. C., et al. (2013) · Oncogenesis · doi:10.1038/oncsis.2013.4 · Cited by 250 · see citing works
Yamaguchi, T., Yanagisawa, K., Sugiyama, R., Hosono, Y., Shimada, Y., Arima, C., Kato, S., Tomida, S., Suzuki, M., Osada, H., et al. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.02.008 · Cited by 249 · cited 1× · see citing works
“1 amplification are activation of ROR1 (which sustains activity of c-Src), kinase activity-independent EGFRERBB3 association, ERBB3 phosphorylation, and consequential PI3K activation [204].”
BackgroundA crucial requirement for Hedgehog signaling in small cell lung cancer
Park, K.-S., Martelotto, L. G., Peifer, M., Sos, M. L., Karnezis, A. N., Mahjoub, M. R., Bernard, K., Conklin, J. F., Szczepny, A., Yuan, J., et al. (2011) · Nature Medicine · doi:10.1038/nm.2473 · Cited by 247 · cited 1× · see citing works
“Deletion of hedgehog- signaling-molecule Smoothened (Smo) halted development of SCLC in a mouse model [226].”
BackgroundCarretero, J., Shimamura, T., Rikova, K., Jackson, A. L., Wilkerson, M. D., Borgman, C. L., Buttarazzi, M., Sanofsky, B. A., McNamara, K. L., Brandstetter, K. A., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.04.026 · Cited by 243 · cited 2× · see citing works
“Integrated analysis of transcriptome and phosphoproteome identified the SRC kinase activation as a frequent event in tumors with LKB1 mutations [170].”
BackgroundMarsit, C. J., Zheng, S., Aldape, K., Hinds, P. W., Nelson, H. H., Wiencke, J. K., & Kelsey, K. T. (2005) · Human Pathology · doi:10.1016/j.humpath.2005.05.006 · Cited by 243 · see citing works
Oncogenic cooperation and coamplification of developmental transcription factor genes in lung cancer
Kendall, J., Liu, Q., Bakleh, A., Alex Krasnitz, A., Nguyen, K. C. Q., Lakshmi, B. V., Gerald, W. L., Powers, S., & Mu, D. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0708286104 · Cited by 236 · cited 1× · see citing works
“1 is amplified in up to 20% of lung adenocarcinoma, but not in SQCC [4, 200, 201].”
BackgroundSos, M. L., Rode, H. B., Heynck, S., Peifer, M., Fischer, F., Klüter, S., Pawar, V. G., Reuter, C., Heuckmann, J. M., Weiss, J., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-3106 · Cited by 220 · cited 1× · see citing works
“But some other results indicate limited activity of the second generation of EGFR inhibitors in the setting of T790 mutation [55, 56].”
BackgroundDallol, A., da Silva, N. F., Viacava, P., Minna, J. D., Bièche, I., Maher, E. R., & Latif, F. (2002) · PubMed · Cited by 215 · see citing works
Socinski, M. A., Goldman, J. W., El‐Hariry, I. A., Koczywas, M., Vukovic, V., Horn, L., Paschold, E., Salgia, R., West, H., Sequist, L. V. D., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-3381 · Cited by 214 · cited 11× · see citing works
“The Hsp90 inhibitor ganetespib, in a preclinical study conducted in vitro and in animals, induced loss of EML4-ALK expression and depletion of multiple oncogenic signaling proteins in ALK-driven NSCLC cells [82].”
BackgroundInfluentialSelf-citationTargeting SOD1 reduces experimental non–small-cell lung cancer
Glasauer, A., Sena, L. A., Diebold, L. P., Mazar, A. P., & Chandel, N. S. (2013) · Journal of Clinical Investigation · doi:10.1172/jci71714 · Cited by 212 · cited 1× · see citing works
“SOD1 inhibitor ATN-224 increases levels of peroxide, activates p38 pathway, and decreases levels of anti-apoptotic protein Mcl1, inducing regression of tumors in a mouse model of NSCLC [198].”
BackgroundFinberg, K. E., Sequist, L. V. D., Joshi, V. A., Muzikansky, A., Miller, J. M., Han, M., Beheshti, J., Chirieac, L. R., Mark, E. J., & Iafrate, A. J. (2007) · Journal of Molecular Diagnostics · doi:10.2353/jmoldx.2007.060182 · Cited by 212 · cited 1× · see citing works
“KRAS mutations are found in majority of mucinous adenocarcinomas [139, 140].”
BackgroundSang, J., Acquaviva, J., Friedland, J. C., Smith, D. L., Sequeira, M., Zhang, C., Jiang, Q., Xue, L., Lovly, C. M., Jimenez, J.-P., et al. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0440 · Cited by 207 · cited 3× · see citing works
“Ganetispib had a greater in vitro potency and better antitumor efficacy compared to crizotinib [82].”
BackgroundEfficacy of BET Bromodomain Inhibition in Kras-Mutant Non–Small Cell Lung Cancer
Shimamura, T., Chen, Z., Soucheray, M., Carretero, J., Kikuchi, E., Tchaicha, J. H., Gao, Y., Cheng, K. A., Cohoon, T. J., Qi, J., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-3904 · Cited by 203 · cited 15× · see citing works
“Expression profiling of these tumors and human lung cancer cell lines identified a variety of metastases-related genes (NEDD9, VEGFC, CD24) as targets of LKB1.”
BackgroundInfluentialReduced NF1 Expression Confers Resistance to EGFR Inhibition in Lung Cancer
de Bruin, E. C., Cowell, C., Warne, P. H., Jiang, M. Z., Saunders, R. E., Melnick, M. A., Gettinger, S. N., Walther, Z., Wurtz, A., Heynen, G. J. J. E., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0741 · Cited by 200 · see citing works
Olivero, M., Rizzo, M., Madeddu, R., Casadio, C., Pennacchietti, S., Nicotra, M., Prat, M., Maggi, G., Arena, N., Natali, P., et al. (1996) · British Journal of Cancer · doi:10.1038/bjc.1996.646 · Cited by 199 · see citing works
Gandhi, L., Bahleda, R., Tolaney, S. M., Kwak, E. L., Cleary, J. M., Pandya, S. S., Hollebecque, A., Abbas, R., Ananthakrishnan, R., Berkenblit, A., et al. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2012.47.2787 · Cited by 198 · cited 1× · see citing works
“A dose-finding study of neratinib combined with temsirolimus produced some clinical responses in HER2 mutant NSCLC patients [110].”
BackgroundWitta, S. E., Jotte, R. M., Konduri, K., Neubauer, M., Spira, A. I., Ruxer, R. L., Varella‐Garcia, M., Bunn, P. A., & Hirsch, F. R. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2011.38.9411 · Cited by 197 · cited 1× · see citing works
“Although the combination regimen did not demonstrate a significant survival advantage in the overall population, it showed a synergistic effect in the subset of patients with high E-cadherin expression [29].”
BackgroundInhibition of KRAS -Driven Tumorigenicity by Interruption of an Autocrine Cytokine Circuit
Zhu, Z., Aref, A. R., Cohoon, T. J., Barbie, T. U., Imamura, Y., Yang, S., Moody, S. E., Shen, R. R., Schinzel, A. C., Thai, T. C., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0646 · Cited by 193 · cited 1× · see citing works
“Compound CYT387 previously known as inhibitor of JAK, is also a potent inhibitor of TBK/IKKα with anti-tumor activity in mouse models [148].”
BackgroundChen, Z., Sasaki, T., Tan, X., Carretero, J., Shimamura, T., Li, D., Xu, C., Wang, Y., Adelmant, G., Capelletti, M., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-1671 · Cited by 192 · cited 1× · see citing works
“However, inhibition of molecular chaperone HSP90 leads to degradation of EML4-ALK and a rapid, but transient, regression of tumor growth in a mouse model [79].”
BackgroundKDM2A promotes lung tumorigenesis by epigenetically enhancing ERK1/2 signaling
Wagner, K. W., Alam, H., Dhar, S. S., Giri, U. P., Li, N., Wei, Y., Giri, D., Cascone, T., Kim, J.-H., Ye, Y., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci68642 · Cited by 191 · cited 1× · see citing works
“High KDM2A levels are associated with low DUSP3, high phospho-ERK levels, and poor prognosis [192].”
BackgroundThomson, S., Petti, F., Sujka-Kwok, I., Epstein, D. M., & Haley, J. D. (2008) · Clinical & Experimental Metastasis · doi:10.1007/s10585-008-9200-4 · Cited by 190 · cited 5× · see citing works
“MET promotes epithelial-mesenchymal transition (EMT), at least in part through activation of SRC. Elevated levels of HGF and intratumoral MET expression have been associated with a more aggressive biology and a worse prognosis in NSCLC. Disregulation of MET pathway leads to cell proliferation, cell survival, angiogene…”
BackgroundInfluentialHuang, S., Li, C., Armstrong, E. A., Peet, C. R., Saker, J., Amler, L. C., Sliwkowski, M. X., & Harari, P. M. (2012) · Cancer Research · doi:10.1158/0008-5472.can-12-1611 · Cited by 190 · cited 2× · see citing works
“Some evidence indicates that targeting other RTKs of the EGFR family in combination with EGFR inhibitors might be efficient in preventing development of resistance [58].”
BackgroundMalanga, D., Scrima, M., Marco, C. D., Fabiani, F., Rosa, N. D., Gisi, S. D., Malara, N., Savino, R., Rocco, G., Chiappetta, G., et al. (2008) · Cell Cycle · doi:10.4161/cc.7.5.5485 · Cited by 190 · see citing works
Jin, G., Kim, M. J., Jeon, H., Choi, J. E., Kim, D. S., Lee, E. B., Ick, S., Yoon, G. S., Kim, C. H., Jung, T. H., et al. (2009) · Lung Cancer · doi:10.1016/j.lungcan.2009.11.012 · Cited by 185 · cited 1× · see citing works
“5% of NSCLC, significantly more frequently in SQCC (10% [163] and 8% [4]).”
BackgroundRequirement for Interaction of PI3-Kinase p110α with RAS in Lung Tumor Maintenance
Castellano, E., Sheridan, C., Thin, M. Z., Nye, E. L., Spencer‐Dene, B., Diefenbacher, M. E., Moore, C., Kumar, M. S., Murillo, M. M., Gronroos, E. C., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.09.012 · Cited by 184 · see citing works
Ethnic Differences and Functional Analysis of MET Mutations in Lung Cancer
Krishnaswamy, S., Kanteti, R., Duke‐Cohan, J. S., Loganathan, S., Liu, W., Ma, P. C., Sattler, M., Singleton, P. A., Ramnath, N., Innocenti, F., et al. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-0070 · Cited by 184 · cited 2× · see citing works
“The MET mutation N375S was detected as a germline mutation in a high proportion of East Asian samples, and was correlated to incidence of squamous-cell carcinoma [89].”
BackgroundSelf-citationOu, S.-H. I. (2012) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2011.11.010 · Cited by 182 · cited 1× · see citing works
“Second-generation EGFR inhibitors that bind to EGFR or other receptors in the EGFR family in an irreversible manner are in clinical testing (reviewed in [20]).”
BackgroundHeinmöller, P., Groß, C., Beyser, K., Schmidtgen, C., Maass, G., Pedrocchi, M., & Rüschoff, J. (2003) · PubMed · Cited by 182 · see citing works
Suehara, Y., Arcila, M. E., Wang, L., Hasanovic, A., Ang, D. C., Ito, T., Kimura, Y., Drilon, A. E. D. C., Guha, U., Rusch, V. W., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-0838 · Cited by 181 · see citing works
Buttitta, F., Barassi, F., Fresu, G., Felicioni, L., Chella, A., Paolizzi, D., Lattanzio, G., Salvatore, S., Camplese, P. P., Rosini, S., et al. (2006) · International Journal of Cancer · doi:10.1002/ijc.22143 · Cited by 180 · see citing works
The EGFR T790M Mutation in Acquired Resistance to an Irreversible Second-Generation EGFR Inhibitor
Kim, Y.-W., Ko, J., Cui, Z.-Y., Abolhoda, A., Ahn, J. S., Ou, S.-H., Ahn, M., & Park, K. (2012) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-11-0750 · Cited by 179 · cited 1× · see citing works
“But some other results indicate limited activity of the second generation of EGFR inhibitors in the setting of T790 mutation [55, 56].”
BackgroundA framework for identification of actionable cancer genome dependencies in small cell lung cancer
Sos, M. L., Dietlein, F., Peifer, M., Schöttle, J., Balke‐Want, H., Müller, C., Koker, M., Richters, A., Heynck, S., Malchers, F., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1207310109 · Cited by 179 · cited 1× · see citing works
“Thus, SCLC with MYC amplification is sensitive to inhibition of aurora kinase B (AURKB) [181].”
BackgroundCardnell, R. J., Feng, Y., Diao, L., Fan, Y.-H., Masrorpour, F., Wang, J., Shen, Y., Mills, G. B., Minna, J. D., Heymach, J. V., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-1975 · Cited by 176 · see citing works
Kim, H. S., Mendiratta, S., Kim, J., Pecot, C. V., Larsen, J. E., Zubovych, I., Seo, B. Y., Kim, J., Eskiocak, B., Chung, H., et al. (2013) · Cell · doi:10.1016/j.cell.2013.09.041 · Cited by 172 · see citing works
Inhibitor-Sensitive FGFR2 and FGFR3 Mutations in Lung Squamous Cell Carcinoma
Liao, R. G., Jung, J., Tchaicha, J. H., Wilkerson, M. D., Sivachenko, A., Beauchamp, E. M., Liu, Q., Pugh, T. J., Pedamallu, C. S., Hayes, D. N., et al. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-3950 · Cited by 168 · cited 1× · see citing works
“Other members of the family (FGFR2 and FGFR3) might be also activated in SQCC at low frequencies of 2% to 3% [4]; mutations in these receptors are oncogenic in vitro and in vivo, and are sensitive to RTK inhibitor pazopanib [129].”
BackgroundShimamura, T., Perera, S. A., Foley, K. P., Sang, J., Rodig, S. J., Inoue, T., Chen, L., Li, D., Carretero, J., Li, Y.-C., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-2967 · Cited by 165 · see citing works
Cardnell, R. J., & Byers, L. A. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-3391 · Cited by 165 · see citing works
Romero, O. A., Torres-Diz, M., Pros, E., Savola, S. P., Gómez, A., Morán, S., Sáez, C., Iwakawa, R., Villanueva, A., Montuenga, L. M., et al. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0799 · Cited by 164 · see citing works
Kim, S., Kim, T. M., Kim, D. W., Go, H., Keam, B., Lee, S., Ku, J., Chung, D. H., & Heo, D. S. (2013) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e318283dcc0 · Cited by 163 · cited 1× · see citing works
“Several patterns were described: secondary (gatekeeper) mutations in ALK that render the kinase resistant to crizotinib; increased ALK copy number, EGFR L858R mutation and high levels of amphiregulin in sera of resistant patients [83].”
BackgroundInhibitors of Hedgehog acyltransferase block Sonic Hedgehog signaling
Petrova, E. P., Rios-Esteves, J., Ouerfelli, O., Glickman, J. F., & Resh, M. D. (2013) · Nature Chemical Biology · doi:10.1038/nchembio.1184 · Cited by 162 · cited 2× · see citing works
“New inhibitors of Hh signaling targeting enzyme HHAT are in development [212].”
BackgroundGordon, M. S., Sweeney, C. J., Mendelson, D. S., Eckhardt, S. G., Anderson, A., Beaupre, D. M., Branstetter, D. G., Burgess, T. L., Coxon, A., Deng, H., et al. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-1365 · Cited by 162 · see citing works
Schaer, D., Budhu, S., Liu, C., Bryson, C. F., Malandro, N., Cohen, A. D., Zhong, H., Yang, X., Houghton, A. N., Merghoub, T., et al. (2013) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-13-0086 · Cited by 160 · cited 1× · see citing works
“Importantly, GITR also negatively affects regulatory T cells (Tregs), and treatment with GITR agonistic antibody destabilizes intra-tumor Tregs allowing for more efficient cytolysis by CD8+ T cells [246].”
BackgroundXian, J., Clark, K. J., Fordham, R., Pannell, R., Rabbitts, T. H., & Rabbitts, P. H. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.251407098 · Cited by 159 · cited 1× · see citing works
“Robo1-deleted mice do not develop normal lungs and most die early after birth; survivors die within the first year of life and show epithelial bronchial hyperplasia [227].”
BackgroundMolina-Arcas, M., Hancock, D. C., Sheridan, C., Kumar, M. S., & Downward, J. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0446 · Cited by 157 · cited 3× · see citing works
“NSCLC lines with activated KRAS depend on the basal IGF1R activity for activation of PI3K pathway [134].”
BackgroundInfluentialZhang, J., Zhang, L., Su, X., Li, M., Xie, L., Malchers, F., Fan, S., Yin, X., Xu, Y., Liu, K., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-2694 · Cited by 156 · cited 1× · see citing works
“FGFR inhibitors PD173074 and AZD4547 inhibit proliferation of SQCC in vitro and tumor growth in vivo [128, 131].”
BackgroundHarnessing the Immune System for the Treatment of Non–Small-Cell Lung Cancer
Brahmer, J. R. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.45.8703 · Cited by 154 · cited 1× · see citing works
“Several vaccines based on different antigens are in trials for lung cancer, including some in phase 3 [248, 249].”
BackgroundZheng, Y., de la Cruz, C. C., Sayles, L. C., Alleyne-Chin, C., Vaka, D., Knaak, T. D., Bigos, M., Xu, Y., Hoang, C. D., Shrager, J. B., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.05.021 · Cited by 154 · cited 1× · see citing works
“, cancer stem cells in NSCLC models, and Notch3, in particular, is nonredundant in KRAS-driven tumors [215].”
BackgroundShapiro, G. I., Rodon, J., Bedell, C., Kwak, E. L., Baselga, J., Braña, I., Pandya, S. S., Scheffold, C., Laird, A. D., Nguyen, L. T., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-1777 · Cited by 152 · cited 1× · see citing works
“Another PI3K inhibitor, SAR245408, has shown promising clinical activity in NSCLC [167].”
BackgroundBehrens, C., Solis, L. M., Lin, H. Y., Yuan, P., Tang, X., Kadara, H. N., Riquelme, E. M., Galindo, H., Moran, C. A., Kalhor, N., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-3946 · Cited by 152 · see citing works
Self-citationLiu, Y., Marks, K. M., Cowley, G. S., Carretero, J., Liu, Q., Nieland, T. J. F., Xu, C., Cohoon, T. J., Gao, P., Zhang, Y., et al. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0015 · Cited by 151 · see citing works
Aerts, J. G. J. V., & Hegmans, J. P. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-3932 · Cited by 148 · see citing works
Burstein, D., Wu, M., Sabo, E., Wang, B., Miller, L. K., Gan, L., & Gil, J. (2003) · American Journal of Clinical Pathology · doi:10.1309/p5ab-r5kq-89rn-jtfh · Cited by 147 · cited 1× · see citing works
“Detection of TP63 by immunostaining is a useful marker that distinguishes lung SQCC from SCLC [217].”
BackgroundUSP8 Is a Novel Target for Overcoming Gefitinib Resistance in Lung Cancer
Byun, S., Lee, S., Lee, J., Jeong, C., Farrand, L., Lim, S., Reddy, K., Kim, J. Y., Lee, M., Lee, H. J., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-3696 · Cited by 147 · cited 1× · see citing works
“Silencing or pharmacological inhibition of USP8 deubiquitinase, relevant in particular to the stability of RTKs such as EGFR and MET, was shown to induce death of gefitinib-resistant NSCLC cells in vitro and in vivo [52].”
BackgroundCharacteristics of Lung Cancers Harboring NRAS Mutations
Ohashi, K., Sequist, L. V. D., Arcila, M. E., Lovly, C. M., Chen, X., Rudin, C. M., Morán, T., Camidge, D. R., Vnencak‐Jones, C. L., Berry, L. D., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-3173 · Cited by 142 · cited 2× · see citing works
“7% and most NRAS-mutated tumors were AC; these had no other driver mutations implicating NRAS in driving tumorigenesis [153].”
BackgroundClinical outcomes in non‐small‐cell lung cancer patients with EGFR mutations: pooled analysis
Paz-Ares, L. G., Soulières, D., Melezínek, I., Moecks, J., Keil, L., Mok, T. S. K., Rosell, R., & Klughammer, B. (2010) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2009.00991.x · Cited by 139 · cited 1× · see citing works
“As noted, EGFR inhibitors have a significantly better effect on PFS compared with conventional chemotherapy [33].”
BackgroundNotch in lung development and lung cancer
Collins, B. J., Kleeberger, W., & Ball, D. W. (2004) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2004.04.015 · Cited by 139 · see citing works
Ascierto, P. A., Kalos, M. D., Schaer, D., Callahan, M. K., & Wolchok, J. D. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-2982 · Cited by 138 · see citing works
KRAS Mutations as Prognostic and Predictive Markers in Non–Small Cell Lung Cancer
Martin, P., Leighl, N. B., Tsao, M., & Shepherd, F. A. (2013) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e318283d958 · Cited by 134 · see citing works
Ramalingam, S. S., Spigel, D. R., Chen, D., Steins, M. B., Engelman, J. A., Schneider, C.-P., Novello, S., Eberhardt, W., Crinò, L., Habben, K., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2011.36.6799 · Cited by 132 · cited 1× · see citing works
“The combination of erlotinib with the IGF1R monoclonal antibody, R1507, did not reveal a statistically significant improvement in PFS or OS in NSCLC [136].”
BackgroundCheung, H. W., Du, J., Boehm, J. S., He, F., Weir, B. A., Wang, X., Butaney, M., Sequist, L. V. D., Luo, B., Engelman, J. A., et al. (2011) · Cancer Discovery · doi:10.1158/2159-8290.cd-11-0046 · Cited by 130 · cited 1× · see citing works
“Another study has identified an acquired amplification of the adaptor protein CRKL (that has known oncogenic properties) in an NSCLC patient that developed resistance to erlotinib [51].”
BackgroundIversen, T. Z., Engell-Noerregaard, L., Ellebæk, E., Andersen, R. S., Larsen, S. K., Bjoern, J., Zeyher, C., Gouttefangeas, C., Thomsen, B. M., Holm, B., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-1560 · Cited by 125 · see citing works
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Lung cancer: Biology and treatment options
Lemjabbar‐Alaoui, H., Hassan, O. U., Yang, Y., & Buchanan, P. C. (2015) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2015.08.002 · Cited by 1,024 · see citing works
“Several targetable genetic alterations have been identified in lung cancer [13] (Table 6), including 1) Activating mutations in a number of proto-oncogenes including KRAS, EGFR, BRAF, PI3K, MEK and HER2.”
BackgroundOsmani, L., Askin, F. B., Gabrielson, E., & Li, Q. K. (2017) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2017.11.019 · Cited by 776 · see citing works
“The development of targeted therapies has advanced the therapeutic strategy from conventional chemo- and radiation-based therapy to genetic alteration-guided targeted therapy [8, 9].”
BackgroundOrganoid Cultures as Preclinical Models of Non–Small Cell Lung Cancer
Shi, R., Radulovich, N., Ng, C., Liu, N., Notsuda, H., Cabanero, M., Martins-Filho, S. N., Raghavan, V., Li, Q., Mer, A. S., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-1376 · Cited by 316 · see citing works
Lung cancer—a fractal viewpoint
Lennon, F. E., Cianci, G. C., Cipriani, N. A., Hensing, T. A., Zhang, H. J., Chen, C.-T., Murgu, S. D., Vokes, E. E., Vannier, M. W., & Salgia, R. (2015) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2015.108 · Cited by 216 · see citing works
Self-citationPharmacological Properties of Geraniol – A Review
Yu, L., Peng, F., Jun, X., & Cheng, P. (2018) · Planta Medica · doi:10.1055/a-0750-6907 · Cited by 187 · see citing works
“Lung cancer ranks first as the cause of mortality among men and third among women worldwide [20].”
Novel therapeutic targets on the horizon for lung cancer
Tan, W.-L., Jain, A., Takano, A. M., Newell, E. W., Iyer, N. G., Lim, W., Tan, E.-H., Zhai, W., Hillmer, A. M., Tam, W. L., et al. (2016) · The Lancet Oncology · doi:10.1016/s1470-2045(16)30123-1 · Cited by 184 · see citing works
Russo, A., Franchina, T., Rita Ricciardi, G. R., Picone, A., Ferraro, G., Zanghì, M., Toscano, G., Giordano, A., & Adamo, V. (2015) · Oncotarget · doi:10.18632/oncotarget.4254 · Cited by 173 · see citing works
“EGFR signaling is commonly deregulated in cancer through different mechanisms, including genetic mutations of the receptor [2, 3].”
BackgroundSarin, N., Engel, F., Kalayda, G. V., Mannewitz, M., Cinatl, J. J., Rothweiler, F., Michaelis, M., Saafan, H., Ritter, C. A., Jaehde, U., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0181081 · Cited by 169 · see citing works
“The mechanisms underlying cisplatin resistance are complex indicating that there is no single mechanism-based strategy to overcome cisplatin resistance [4,7,8].”
BackgroundQaiser, T., Mukherjee, A., Chaitanya Reddy, P. B., Munugoti, S. D., Vamsi, T., Pitkäaho, T., Lehtimäki, T., Naughton, T. J., Berseth, M., Pedraza, A., et al. (2017) · Histopathology · doi:10.1111/his.13333 · Cited by 162 · see citing works
“Other possible extensions of digital pathology could be to automate the overexpression of the programmed death 1 (PD-1) receptor and its ligand (PD-L1) to evaluate anaplastic lymphoma kinase (ALK) protein and proto-oncogene tyrosine-protein kinase ROS1 in lung cancers.(17) The AIbased algorithms would be more effectiv…”
MethodAlessi, J. V., Ricciuti, B., Spurr, L. F., Gupta, H. V., Li, Y. Y., Glass, C., Nishino, M., Cherniack, A. D., Lindsay, J. R., Sharma, B., et al. (2021) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2021.03.024 · Cited by 156 · see citing works
Cellular senescence in lung cancer: Molecular mechanisms and therapeutic interventions
Jha, S. K., Rubis, G. D., Devkota, S. R., Zhang, Y., Adhikari, R., Jha, L. A., Bhattacharya, K., Mehndiratta, S., Gupta, G., Singh, S. K., et al. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102315 · Cited by 122 · see citing works
“One of the deadliest diseases with a high death rate is lung cancer, which also happens to be the most common cause of tumor-related deaths (Global Burden of Disease Cancer et al., 2015; Shtivelman et al., 2014).”
Afatinib for the treatment of <i>EGFR</i> mutation-positive NSCLC: A review of clinical findings
Harvey, R. D., Adams, V. R., Beardslee, T., & Medina, P. (2020) · Journal of Oncology Pharmacy Practice · doi:10.1177/1078155220931926 · Cited by 115 · see citing works
Cancer stem cells and immunoresistance: clinical implications and solutions.
Codony‐Servat, J., & Rosell, R. (2015) · PubMed Central · doi:10.3978/j.issn.2218-6751.2015.12.11 · Cited by 112 · see citing works
“A phase III clinical trial is ongoing (85,123).”
BackgroundMethodInfluentialLiu, H., Gu, Y., Wang, H., Yin, J., Zheng, G., Zhang, Z., Lu, M., Wang, C., & He, Z. (2015) · Oncotarget · doi:10.18632/oncotarget.3818 · Cited by 94 · see citing works
“In spite of advances in developing more efficient surgical techniques and novel chemotherapeutic interventions, as well as targeted therapies, the longterm survival rate of NSCLC patients remains poor [2, 3].”
MiR-150 promotes cellular metastasis in non-small cell lung cancer by targeting FOXO4
Li, H., Ouyang, R., Wang, Z., Zhou, W., Chen, H., Jiang, Y., Zhang, Y., Li, H., Liao, M., Wang, W., et al. (2016) · Scientific Reports · doi:10.1038/srep39001 · Cited by 92 · see citing works
Li, X., Li, Z. S., Wu, X., Xiong, Z., Yang, T., Fu, Z., Liu, X., Tan, X., Zhong, F., Wan, X., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b00855 · Cited by 93 · see citing works
Na/K Pump and Beyond: Na/K-ATPase as a Modulator of Apoptosis and Autophagy
Gonçalves-de-Albuquerque, C. F., Silva, A. R., da Silva, C. I., Castro-Faria-Neto, H. C., & Burth, P. (2017) · Molecules · doi:10.3390/molecules22040578 · Cited by 89 · see citing works
Quantification of mutant alleles in circulating tumor DNA can predict survival in lung cancer
Yang, X., Zhuo, M., Ye, X., Bai, H., Wang, Z., Sun, Y., Zhao, J., An, T., Duan, J., Wu, M., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.8021 · Cited by 78 · see citing works
Shoja, Y., Kermanpur, A., & Karimzadeh, F. (2018) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2018.04.013 · Cited by 76 · see citing works
Han, L., Sheng, B., Zeng, Q., Yao, W., & Jiang, Q. (2020) · BMC Pulmonary Medicine · doi:10.1186/s12890-020-01317-1 · Cited by 75 · see citing works
Bria, E., Pilotto, S., Amato, E., Fassan, M., Novello, S., Peretti, U., Vavalà, T., Kinspergher, S., Righi, L., Santo, A., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.3727 · Cited by 73 · see citing works
“TP53 represents the most frequently mutated gene in lung cancer, occurring in over half of adenocarcinoma, 80% of squamous cell carcinoma and 70% of small-celllung cancer [15].”
BackgroundGenome sequencing analysis of liver cancer for precision medicine
Nakagawa, H., Fujita, M., & Fujimoto, A. (2018) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2018.03.004 · Cited by 72 · see citing works
Langer, C. J., Obasaju, C. K., Bunn, P. A., Bonomi, P., Gandara, D. R., Hirsch, F. R., Kim, E. S., Natale, R. B., Novello, S., Paz-Ares, L. G., et al. (2016) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2016.08.138 · Cited by 64 · see citing works
“Selected signaling pathwayswith actionablemolecular t targeted agents approved or in development.(21,25,125) RTK, recep noblastoma; ErbB2/3, erb-b2 receptor tyrosine kinase 2/3; FGFR ceptor tyrosine kinase 2; PIK3CA, phosphatidylinositol 3-kinase ca AKT, alpha serine/threonine-protein kinase; CDKN2A, cyclin-depen and…”
BackgroundKim, S. M., Shin, S. C., Kim, E. E., Kim, S., Park, K., Oh, S. J., & Jang, M. (2018) · ACS Nano · doi:10.1021/acsnano.8b01670 · Cited by 63 · see citing works
Riaz, M. A., Sak, A., Erol, Y. B., Groneberg, M., Thomale, J., & Stuschke, M. (2019) · Scientific Reports · doi:10.1038/s41598-018-38004-5 · Cited by 62 · see citing works
Advances in Small-Cell Lung Cancer (SCLC) Translational ResearchPreprint
Drapkin, B. J., & Rudin, C. M. (2020) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a038240 · Cited by 61 · see citing works
Catacchio, I., Scattone, A., Silvestris, N., & Mangia, A. (2018) · Translational Oncology · doi:10.1016/j.tranon.2018.04.006 · Cited by 58 · see citing works
Lidocaine inhibits the proliferation of lung cancer by regulating the expression of GOLT 1A
Zhang, L., Hu, R., Cheng, Y., Wu, X., Xi, S., Sun, Y., & Jiang, H. (2017) · Cell Proliferation · doi:10.1111/cpr.12364 · Cited by 59 · see citing works
Lin, C., Wang, S., Xie, W., Zheng, R., Gan, Y., & Chang, J. (2016) · Oncotarget · doi:10.18632/oncotarget.10985 · Cited by 55 · see citing works
“Identification of oncogenic drivers has been highlighted in the era of precision medicine [5].”
BackgroundInteractions Between Tumor Biology and Targeted Nanoplatforms for Imaging Applications
Azizi, M., Dianat‐Moghadam, H., Salehi, R., Farshbaf, M., Iyengar, D., Sau, S., Iyer, A. K., Valizadeh, H., Mehrmohammadi, M., & Hamblin, M. R. (2020) · Advanced Functional Materials · doi:10.1002/adfm.201910402 · Cited by 55 · see citing works
Lin, C., Wang, S., Xie, W., Chang, J., & Gan, Y. (2015) · Cancer Biology & Therapy · doi:10.1080/15384047.2015.1046649 · Cited by 53 · see citing works
“Generally, translocations are observed in a higher percentage in young and adenocarcinoma patients.(26) However, there are discrepancies among other factors like sex, age, tumor size and stage.”
BackgroundMa, Y., Feng, W., Wu, Z., Liu, M., Zhang, F., Liang, Z., Cui, C., Huang, J., Li, X., & Guo, X. (2018) · Physics in Medicine and Biology · doi:10.1088/1361-6560/aad648 · Cited by 53 · see citing works
Detection EGFR exon 19 status of lung cancer patients by DNA electrochemical biosensor
Xu, X., Weng, X., Wang, C., Lin, W.-W., Liu, A., Chen, W., & Lin, X. (2016) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2016.02.009 · Cited by 52 · see citing works
“Lung cancer, the leading cause of cancer death, accounts for about one third of all cancer mortality worldwide due to its high incidence, aggressive tumors behavior, and advanced stage at diagnosis (Shtivelman et al., 2014).”
BackgroundNon-Coding RNAs in Lung Tumor Initiation and Progression
Santos, R. M., Moreno, C., & Zhang, W. C. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21082774 · Cited by 48 · see citing works
“Wnt/β-Catenin The Wnt/β-catenin (canonical) pathway holds the responsibility of determining cell polarity, rate of proliferation, and the fate of the cell [258].”
BackgroundInfluentialCurrent Drugs and Drug Targets in Non-Small Cell Lung Cancer: Limitations and Opportunities
Daga, A., Ansari, A., Patel, S., Mirza, S., Rawal, R., & Umrania, V. V. (2015) · Asian Pacific Journal of Cancer Prevention · doi:10.7314/apjcp.2015.16.10.4147 · Cited by 47 · see citing works
“These oncogenic driver mutations activate signaling cascades in constitutive manner leading to uncontrolled cell growth and proliferation (Pao and Girard, 2011; Cooper et al., 2013; Shtivelman et al., 2014).”
BackgroundLiu, F., Song, D., Wu, Y., Liu, X., Zhu, J., & Tang, Y. (2017) · Thoracic Cancer · doi:10.1111/1759-7714.12492 · Cited by 47 · see citing works
Piao, J., Sun, J. L., Yang, Y., Jin, T., Chen, L., & Lin, Z. (2018) · Gene · doi:10.1016/j.gene.2018.01.003 · Cited by 47 · see citing works
“more than one million deaths per year (Califano et al., 2012; Shtivelman et al., 2014).”
BackgroundZhang, P., Kang, B., Xie, G., Li, S., Gu, Y., Shen, Y., Zhao, X., Ma, Y., Li, F., Si, J., et al. (2018) · Cancer Letters · doi:10.1016/j.canlet.2018.10.035 · Cited by 47 · see citing works
Kinases inhibitors in lung cancer: From benchside to bedside
Singh, P. K., Singh, H., & Silakari, O. (2016) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2016.07.002 · Cited by 46 · see citing works
Shi, Y., Li, J., Lai, X., Jiang, R., Zhao, R., & Xiong, L. (2020) · Cancers · doi:10.3390/cancers12020291 · Cited by 46 · see citing works
“Targeted drugs aimed at EGFR mutation, regarded as EGFR tyrosine kinase inhibitors (EGFR-TKI), are also well studied [128].”
BackgroundZito, G., Naselli, F., Saieva, L., Raimondo, S., Calabrese, G., Guzzardo, C., Forte, S., Rolfo, C. D., Parenti, R., & Alessandro, R. (2017) · Scientific Reports · doi:10.1038/s41598-017-05047-z · Cited by 41 · see citing works
Piao, J., Chen, L., Quan, T., Li, L.-S., Quan, C., Piao, Y., Jin, T., & Lin, Z. (2016) · Oncotarget · doi:10.18632/oncotarget.11109 · Cited by 40 · see citing works
“NSCLC is the major histological form of epithelial lung cancer, and it remains the principle cause of cancer-related death, accounting for more than one million deaths per year [2, 3].”
BackgroundSu, B., Lai, J., Lin, H., Luo, X., Zeng, Y., & Du, T. (2021) · Journal of Pharmacy and Pharmacology · doi:10.1093/jpp/rgab056 · Cited by 40 · see citing works
Alghamdi, R. A., & Al-Zahrani, M. H. (2023) · Saudi Journal of Biological Sciences · doi:10.1016/j.sjbs.2023.103596 · Cited by 39 · see citing works
Key Players of Cisplatin Resistance: Towards a Systems Pharmacology Approach
Sarin, N., Engel, F., Rothweiler, F., Cinatl, J. J., Michaelis, M., Frötschl, R., Fröhlich, H., & Kalayda, G. V. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19030767 · Cited by 39 · see citing works
“Signalling pathways, like extracellular-signal regulated kinase (ERK1/2), phosphatidylinositide-3-kinase/protein kinase B (PI3K/Akt) or P38 mitogen-activated protein kinases (p38MAPK) pathway are involved in the cellular reaction to cisplatin treatment [2,3].”
BackgroundLymphocyte percentage as a valuable predictor of prognosis in lung cancer
Huang, H., Li, L., Luo, W., Yang, Y., Ni, Y., Song, T., Zhu, Y., Yang, Y., & Zhang, L. (2022) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.17214 · Cited by 38 · see citing works
Critical role of miR-155/FoxO1/ROS axis in the regulation of non-small cell lung carcinomas
Hou, L., Chen, J., Zheng, Y., & Wu, C. (2015) · Tumor Biology · doi:10.1007/s13277-015-4335-9 · Cited by 38 · see citing works
“The main types of NSCLC are adenocarcinoma and squamous cell carcinoma [3].”
BackgroundManafi‐Farid, R., Ziarati, N. K., Vali, R., Mottaghy, F. M., & Beheshti, M. (2020) · Methods · doi:10.1016/j.ymeth.2020.05.023 · Cited by 37 · see citing works
miR-433 suppresses tumor progression via Smad2 in non-small cell lung cancer
Li, J., Chen, M., & Yu, B. (2019) · Pathology - Research and Practice · doi:10.1016/j.prp.2019.152591 · Cited by 37 · see citing works
The roles of ARHGAP10 in the proliferation, migration and invasion of lung cancer cells
Teng, J., Yang, Z., Zhu, Y., Ni, D., Zhu, Z., & Li, X. (2017) · Oncology Letters · doi:10.3892/ol.2017.6729 · Cited by 36 · see citing works
“The molecular mechanisms of lung carcinogenesis have yet to be completely clarified (3-7).”
Interactions of quercetin with receptor tyrosine kinases associated with human lung carcinoma
Baby, B., Antony, P., & Vijayan, R. (2017) · Natural Product Research · doi:10.1080/14786419.2017.1385015 · Cited by 36 · see citing works
“…growth factor 1 receptor (IGF1R) and tyrosine-protein kinase Met (MET) were observed to be overexpressed in lung cancer cell lines while others were either mutated or translocated (Selvaggi et al. 2004; Velcheti and Govindan 2006; Gelsomino et al. 2014; Shtivelman et al. 2014; Theelen et al. 2016).”
BackgroundEYA2 promotes lung cancer cell proliferation by downregulating the expression of PTEN
Li, Z., Qiu, R., Qiu, X., & Tian, T. (2017) · Oncotarget · doi:10.18632/oncotarget.22860 · Cited by 36 · see citing works
Juglanin inhibits lung cancer by regulation of apoptosis, ROS and autophagy induction
Chen, L., Xiong, Y., Xu, J., Wang, J., Meng, Z., & Hong, Y. (2017) · Oncotarget · doi:10.18632/oncotarget.21317 · Cited by 35 · see citing works
“Among lung cancer patients, NSCLS accounts for about 85% of the cases, being the most common one [2, 53].”
BackgroundWang, F., Wang, S., Xue, W., & Cheng, J. (2016) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-016-2822-y · Cited by 34 · see citing works
“Considerable efforts have been made to uncover the key regulatory molecules in NSCLC development and progression [22].”
BackgroundSong, F., Song, X., Feng, Y., Fan, G., Sun, Y., Zhang, P., Li, J., Liu, F., & Zhang, G. (2023) · Medical Physics · doi:10.1002/mp.16233 · Cited by 33 · see citing works
Papini, F., Sundaresan, J., Leonetti, A., Tiseo, M., Rolfo, C. D., Peters, G. J., & Giovannetti, E. (2021) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2021.103454 · Cited by 35 · see citing works
Adapt, Recycle, and Move on: Proteostasis and Trafficking Mechanisms in Melanoma
Demirsoy, Ş., Martín-Acebes, M. A., Maes, H., & Agostinis, P. (2016) · Frontiers in Oncology · doi:10.3389/fonc.2016.00240 · Cited by 33 · see citing works
Fatai, A. A., & Gamieldien, J. (2018) · BMC Cancer · doi:10.1186/s12885-018-4103-5 · Cited by 32 · see citing works
Non-coding RNA and lung cancer progression
Ishola, A. A., La’ah, A. S., Le, H. D., Nguyen, V. Q., Yang, Y., Chou, S., Tai, H., Chien, C., & Wang, M. (2019) · Journal of the Chinese Medical Association · doi:10.1097/jcma.0000000000000225 · Cited by 32 · see citing works
CDKN1A upregulation and cisplatin‑pemetrexed resistance in non‑small cell lung cancer cells
Zamagni, A., Pasini, A., Pirini, F., Ravaioli, S., Giordano, E., Tesei, A., Calistri, D., Ulivi, P., Fabbri, F., Foca, F., et al. (2020) · International Journal of Oncology · doi:10.3892/ijo.2020.5024 · Cited by 32 · see citing works
“The mechanism of action of cisplatin relies on the induction of DNA damage (12), resulting in cell cycle arrest and subsequent apoptosis.”
Lv, L., Zhang, W., Li, T., Jiang, L., Lu, X., & Lin, J. (2020) · Oncology Reports · doi:10.3892/or.2020.7568 · Cited by 32 · see citing works
“Non-small cell lung cancer (NSCLC) constitutes 80-85% of all lung cancer cases, with squamous cell carcinoma and adenocarcinoma as the two major subtypes (3).”
BackgroundMachine learning for genomic profiling and drug discovery in personalised lung cancer therapeutics
Ahmad, S., Shah, S. N. A., Parveen, R., & Raza, K. (2025) · Journal of drug targeting · doi:10.1080/1061186x.2025.2530656 · Cited by 33 · see citing works
“…its molecular mechanisms, heterogeneity and evolution, factors driving tumour initiation, progression and response to therapy. the genome-level cause of lung cancer, exploring the key genetic factors and their implications for diagnosis, prognosis and treatment, are discussed below [46].”
Stanzione, M., Zhong, J., Wong, E., LaSalle, T. J., Wise, J. F., Simoneau, A., Myers, D. T., Phat, S., Sade-Feldman, M., Lawrence, M. S., et al. (2022) · Science Advances · doi:10.1126/sciadv.abn1229 · Cited by 31 · see citing works
Muthuramalingam, P., Akassh, S., Rithiga, S. B., Prithika, S., Gunasekaran, R., Shin, H., Kumar, R., Venkidasamy, B., & Kim, J. (2022) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2022.175479 · Cited by 31 · see citing works
Gene regulatory networks reveal sex difference in lung adenocarcinoma
Saha, E., Guebila, M. B., Fanfani, V., Fischer, J., Shutta, K. H., Mandros, P., DeMeo, D. L., Quackenbush, J. F., & Lopes‐Ramos, C. M. (2024) · Biology of Sex Differences · doi:10.1186/s13293-024-00634-y · Cited by 33 · see citing works
“To understand how differential regulation of specific drug targets might contribute towards different efficacy of various cancer drugs in males and females with LUAD, we chose 28 genes commonly targeted by lung cancer drugs [31] for an in-depth analysis (Fig.”
BackgroundWang, Z., Ma, B., Li, H., Xiao, X., Zhou, W., Liu, F., Zhang, B., Zhu, M. P., Yang, Q., Zeng, Y., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.6312 · Cited by 29 · see citing works
“To improve the survival of NSCLC patients, the screening for growth and metastasis-related genes in lung cancer has significant value for prognosis and targeted therapy [2].”
BackgroundPRMT5 Selective Inhibitor Enhances Therapeutic Efficacy of Cisplatin in Lung Cancer Cells
Bajbouj, K., Ramakrishnan, R. K., Saber-Ayad, M. M., Omar, H. A., Sharif‐Askari, N. S., Shafarin, J., Elmoselhi, A. B., M.H.Ihmaid, A., Ali, S. A., Alalool, A., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22116131 · Cited by 29 · see citing works
“Various proteins, genes, or pathways were found to be involved in resistance against cisplatin [34,35].”
BackgroundChary, P. S., Bhawale, R., Vasave, R., Rajana, N., Singh, P. K., Madan, J., Singh, S. B., & Mehra, N. K. (2023) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2023.104588 · Cited by 29 · see citing works
Wei, G., Xu, Y., Peng, T., Yan, J., Wang, Z., & Sun, Z. (2017) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.21914 · Cited by 29 · see citing works
Chen, J., Sun, Y., Chen, Q., Wang, L., Wang, S. H., Tang, Y., Shi, X., & Wang, H. (2016) · Nanoscale · doi:10.1039/c6nr03143a · Cited by 27 · see citing works
Targeted depletion of PIK3R2 induces regression of lung squamous cell carcinoma
Vallejo-Díaz, J., Olazabal-Morán, M., Cariaga-Martínez, A. E., Pajares, M. J., Flores, J. M., Pı́o, R., Montuenga, L. M., & Carrera, A. C. (2016) · Oncotarget · doi:10.18632/oncotarget.13195 · Cited by 27 · see citing works
He, M., & Xue, Y. (2017) · OncoTargets and Therapy · doi:10.2147/ott.s123518 · Cited by 27 · see citing works
“Keywords: miR-148a, STAT3, non-small cell lung carcinomas, cell proliferation, invasion Introduction It is well known that lung cancer has the highest morbidity and mortality in the world.1,2 It has been reported that lung cancer resulted in 160,000 deaths in the United States in 2014, which accounted for 20% of all c…”
InfluentialLuo, H., & Liang, C. (2018) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2018.5845 · Cited by 26 · see citing works
“Out of all lung cancer-associated mortalities, ~80% occurred in patients with NSCLC (3-5) and the main types of NSCLC include adenocarcinoma and squamous cell carcinoma (6).”
Lei, Z., Shi, H., Li, W., Yu, D., Shen, F., Yu, X. Y., Lü, D., Sun, C., & Liao, K. (2017) · Molecular Medicine Reports · doi:10.3892/mmr.2017.8050 · Cited by 26 · see citing works
“Lung cancer consists of two principal types: Small-cell lung carcinoma, and non-small-cell lung carcinoma (NSCLC), accounting for ~15 and 85% of all cases of lung cancer, respectively (3,4).”
Salgia, R. (2016) · Expert Review of Molecular Diagnostics · doi:10.1080/14737159.2016.1181545 · Cited by 25 · see citing works
“With dozens of known targets and many agents approved or in development, there are a large number of possible combinations and sequences that can potentially be investigated or deployed in to treat or prevent drug-resistant patients in the clinic, often with support from preclinical models [144].”
BackgroundSelf-citationYang, L., Wei, S., Zhang, J., Hu, Q., Hu, W., Cao, M., Zhang, L., Wang, Y., Wang, P., & Wang, K. (2022) · Journal of Translational Medicine · doi:10.1186/s12967-022-03565-7 · Cited by 25 · see citing works
“Compared with lung adenocarcinoma, LUSC has a low rearrangement rate of EGFR gene mutation and ALK fusion gene, and strong tumor heterogeneity [5], Therefore, LUSC is limited in gene mutation-based targeted therapy applications [6, 7].”
BackgroundHowells, L. M., Mahale, J., Sale, S., McVeigh, L. E., Steward, W. P., Thomas, A., & Brown, K. (2014) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.114.216333 · Cited by 24 · see citing works
“anaplastic lymphoma kinase fusions, which are altered in approximately 25% of adenocarcinomas (Shtivelman et al., 2014).”
BackgroundStorti, C. B., de Oliveira, R. A., de Carvalho, M., Hasimoto, É. N., Catâneo, D. C., Catâneo, A. J. M., Faveri, J. D., Vasconcelos, E. J. R., Reis, P. P., & Cano, M. I. N. (2019) · Experimental and Molecular Pathology · doi:10.1016/j.yexmp.2019.104354 · Cited by 24 · see citing works
Xu, L., Xu, Y., Yang, M., Li, J., Xu, F., & Chen, B. (2020) · BMC Pulmonary Medicine · doi:10.1186/s12890-020-01276-7 · Cited by 24 · see citing works
Zhang, X., Dong, Y., Gao, M., Hao, M., Ren, H., Guo, L., & Guo, H. (2020) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-020-03973-7 · Cited by 24 · see citing works
RetractedPan, S., Su, K., Spiessens, B., Kusuma, N., Delahaye, N. F., Gruselle, O., Myo, A., Creus, A. D., Louahed, J., Chang, G.-C., et al. (2016) · Asia-Pacific Journal of Clinical Oncology · doi:10.1111/ajco.12586 · Cited by 23 · see citing works
EGFR and COX-2 Dual Inhibitor: The Design, Synthesis, and Biological Evaluation of Novel Chalcones
Musa, A., Mostafa, E. M., Bukhari, S. N. A., Alotaibi, N. H., El-Ghorab, A. H., Farouk, A., Nayl, A. A., Ghoneim, M. M., & Abdelgawad, M. A. (2022) · Molecules · doi:10.3390/molecules27041158 · Cited by 23 · see citing works
“This activates a number of downstream pathways that control cell processes such as DNA synthesis and proliferation [10,11].”
BackgroundComprehensive transcriptomic analysis identifies novel regulators of lung adenocarcinoma
Mokhlesi, A., & Talkhabi, M. (2020) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-020-00565-4 · Cited by 23 · see citing works
“Several NSCLC inducing mutations have been found in some important factors including epidermal growth factor receptor (EGFR), parallel phosphatidylinositol 3-kinase (PI3K) pathway and mitogen-activated protein kinase kinase (MAP2K1) (Shtivelman et al. 2014; Nicetto and Zaret 2019).”
BackgroundGristina, V., Mantia, M. L., Galvano, A., Cutaia, S., Barraco, N., Castiglia, M., Perez, A., Bono, M., Iacono, F., Greco, M., et al. (2021) · Journal of Molecular Pathology · doi:10.3390/jmp2020016 · Cited by 23 · see citing works
Sato, T., Takagi, K., Higuchi, M., Abe, H., Kojimahara, M., Sagawa, M., Tanaki, M., Miki, Y., Suzuki, T., & Hojo, H. (2022) · ACTA HISTOCHEMICA ET CYTOCHEMICA · doi:10.1267/ahc.21-00075 · Cited by 22 · see citing works
Song, F., Tian, J., Zhang, P., Ma, C., Sun, Y., Feng, Y., Zhang, T., Lei, Y., He, Y., Cai, Z., et al. (2023) · IEEE Journal of Biomedical and Health Informatics · doi:10.1109/jbhi.2023.3290006 · Cited by 22 · see citing works
“In clinical practice, before the establishment of patient treatment plan, accurate histological subtype information of NSCLC should be determined [34], [35].”
BackgroundmiR-16-1-3p targets TWIST1 to inhibit cell proliferation and invasion in NSCLC
Feng, Q. Q., Dong, Z., Zhou, Y., Zhang, H., & Long, C. (2018) · Bratislavské lekárske listy/Bratislava medical journal · doi:10.4149/bll_2018_012 · Cited by 22 · see citing works
“It is reported that approximately 80% of lung cancer refers to non-small cell lung cancer (NSCLC), which includes adenocarcinoma (AC), squamous cell carcinoma (SQCC) and large cell carcinoma (LCLC) (3).”
Sharma, R. B., Wang, Y., Chen, L., Gurda, G. T., Geddes, S., Gabrielson, E., Askin, F. B., & Li, Q. K. (2016) · Human Pathology · doi:10.1016/j.humpath.2016.02.027 · Cited by 21 · see citing works
“Therefore, accurate histologic subclassification and molecular characterization of NSCLC play a critical role in the delivery of targeted therapies [2,3,13–15].”
BackgroundChoi, S., Lee, J.-H., Kim, R.-K., Jung, U., Kahm, Y.-J., Cho, E., & Kim, I. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186957 · Cited by 21 · see citing works
“Among cancers, lung cancer has a high mortality rate, so new therapeutic strategies are required [8].”
BackgroundRottlerin exhibits antitumor activity via down-regulation of TAZ in non-small cell lung cancer
Zhao, Z., Zheng, N., Wang, L., Hou, Y., Zhou, X., & Wang, Z. P. (2016) · Oncotarget · doi:10.18632/oncotarget.13974 · Cited by 20 · see citing works
“Multiple treatments have been applied for NSCLC patients including pneumonectomy, radiation, chemotherapy, or combined modalities [3, 4].”
MethodA proteomic profiling of laser‐microdissected lung adenocarcinoma cells of early lepidic‐types
Kato, Y., Nakamura, H., Tojo, H., Nomura, M., Nagao, T., Kawamura, T., Kodama, T., Ohira, T., Ikeda, N., Fehniger, T. E., et al. (2015) · Clinical and Translational Medicine · doi:10.1186/s40169-015-0064-3 · Cited by 20 · see citing works
“Over-expression of EGFR occurs around 60 % of non-small cell lung cancer (NSCLC), in which adenocarcinoma has the higher frequency [35].”
BackgroundDanish, L., Imig, D., Allgöwer, F., Scheurich, P., & Pollak, N. (2018) · PLoS ONE · doi:10.1371/journal.pone.0198203 · Cited by 19 · see citing works
Meister, K. D., Godse, N. R., Khan, N. I., Hedberg, M. L., Kemp, C., Kulkarni, S., Alvarado, D., LaVallee, T. M., Kim, S., Grandis, J. R., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-45589-y · Cited by 19 · see citing works
The Role of Hydrogen Sulfide in the Development and Progression of Lung Cancer
Yang, Y., Zhang, K., Zhou, Z.-T., Jiang, Z.-L., Liu, Y., Zhang, Y., Liu, Z., Ji, X., & Wu, D. (2022) · Molecules · doi:10.3390/molecules27249005 · Cited by 19 · see citing works
“The activation of caspase and the activities of PI3K/Akt, MAPK/ERK, MAPK/JNK, and MAPK/p38 pathways play an important role in the proliferation and metastasis of cancer cells [85].”
BackgroundCurrent status of clinical proteogenomics in lung cancer
Nishimura, T., Nakamura, H., Végvári, Á., Marko‐Varga, G., Furuya, N., & Saji, H. (2019) · Expert Review of Proteomics · doi:10.1080/14789450.2019.1654861 · Cited by 19 · see citing works
“mutated genes, such as SMARCA4, MILL2, and EP300, respectively [109].”
BackgroundInfluentialZhou, H., Zhang, H., Shi, M., Wang, J., Huang, Z., & Shi, J. (2020) · International Immunopharmacology · doi:10.1016/j.intimp.2020.106856 · Cited by 18 · see citing works
Feng, Y., Li, C., Liu, S., Yan, F., Teng, Y., Li, X., & Sun, Y. (2022) · Journal of Oncology · doi:10.1155/2022/3472745 · Cited by 18 · see citing works
“Additionally, due to the lack of the potent biomarkers in the diagnosis and therapy of lung cancer, its 5-year survival rate remains far from satisfactory for all stages [34].”
BackgroundRetractedJingwen, E., Liu, Y., Guan, S., Luo, Z., Han, F., Han, W., Wang, S., & Zhang, H. (2020) · Molecules · doi:10.3390/molecules25040895 · Cited by 18 · see citing works
“The pathogenesis of non-small cell lung cancer (NSCLC) is closely related to the mutant kinase activity in epidermal growth factor receptor (EGFR) [1,2], while abnormal signal transduction is closely related to the occurrence of cancer;”
BackgroundTetrahydro-3 H -pyrazolo[4,3- a ]phenanthridine-based CDK inhibitor
Opoku‐Temeng, C., Dayal, N., Hernandez, D. E., Naganna, N., & Sintim, H. O. (2018) · Chemical Communications · doi:10.1039/c8cc01154k · Cited by 18 · see citing works
Polo, V., Pasello, G., Frega, S., Favaretto, A. G., Koussis, H., Conte, P., & Bonanno, L. (2016) · Oncotarget · doi:10.18632/oncotarget.7732 · Cited by 17 · see citing works
“In the latest years several efforts have been made to introduce genomic tests and targeted therapies in cancer treatment [56-59].”
Background
- Authors
- Shtivelman, E., Hensing, T., Simon, G. R., Dennis, P. A., Otterson, G. A., Bueno, R., & Salgia, R.
- Affiliations
- Cancer Commons, Palo Alto, CA, United States of America
- Endeavor Health (US)
- The University of Texas MD Anderson Cancer Center (US)
- Johns Hopkins University (US)
- The Ohio State University (US)
- Brigham and Women's Hospital (US)
- University of Chicago (US)
- Venue
- Oncotarget
- Publisher
- Impact Journals, LLC
- Published
- 2014-03-30
- Volume
- 5
- Issue
- 6
- Pages
- 1392-1433
- ISSN
- 1949-2553 (ISSN-L)
- PMC
- PMC4039220
- OpenAlex
- W2146633923
- Cited by
- 220
- References
- 263
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 15 · 2023: 16 · 2022: 22 · 2021: 13 · 2020: 22 · 2019: 22 · 2018: 21 · 2017: 24 · 2016: 29 · 2015: 15 · 2014: 4
- FWCI
- 4.10
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by
- Locations
- Oncotarget (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Keywords
- lung cancer, molecular pathways, therapeutic target, targeted therapy, immunotherapy, non-small cell lung cancer, lung adenocarcinoma, lung squamous cell carcinoma, small cell lung cancer, molecular alterations, clinical trials
- MeSH terms
- Animals, Antineoplastic Agents, Humans, Neoplasm Proteins, Neoplasms, Signal Transduction, Molecular Targeted Therapy
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