PTEN Loss Contributes to Erlotinib Resistance in EGFR-Mutant Lung Cancer by Activation of Akt and EGFR
Open accessPublished version of a preprint
Abstract
Clinical resistance to epidermal growth factor receptor (EGFR) inhibition in lung cancer has been linked to the emergence of the EGFR T790M resistance mutation or amplification of MET. Additional mechanisms contributing to EGFR inhibitor resistance remain elusive. By applying combined analyses of gene expression, copy number, and biochemical analyses of EGFR inhibitor responsiveness, we identified homozygous loss of PTEN to segregate EGFR-dependent and EGFR-independent cells. We show that in EGFR-dependent cells, PTEN loss partially uncouples mutant EGFR from downstream signaling and activates EGFR, thereby contributing to erlotinib resistance. The clinical relevance of our findings is supported by the observation of PTEN loss in 1 out of 24 primary EGFR-mutant non-small cell lung cancer (NSCLC) tumors. These results suggest a novel resistance mechanism in EGFR-mutant NSCLC involving PTEN loss.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
PTEN loss may be associated with resistance to EGFR inhibitors.
“Similarly, a report found that PTEN loss may be associated with resistance to EGFR inhibitors (Sos et al., 2009).”
From ERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics (2014) · cites this paper as Sos et al., 2009
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Somatic 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 · see citing works
Self-citationNegative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN
Stambolic, V., Suzuki, A., de la Pompa, J. L., Brothers, G. M., Mirtsos, C., Sasaki, T., Ruland, J., Penninger, J. M., Siderovski, D. P., & Mak, T. W. (1998) · Cell · doi:10.1016/s0092-8674(00)81780-8 · Cited by 2,551 · see citing works
Global 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 · see citing works
Bean, 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 · see citing works
Self-citationMolecular determinants of the response of glioblastomas to EGFR kinase inhibitors
Mellinghoff, I. K., Wang, M. Y., Vivanco, I., Haas-Kogan, D. A., Zhu, S., Dia, E. Q., Lu, K. V., Yoshimoto, K., Huang, J. H. Y., Chute, D. J., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa051918 · Cited by 1,442 · see citing works
Characterizing 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 · see citing works
The Biology and Clinical Relevance of the PTEN Tumor Suppressor Pathway
Sansal, I., & Sellers, W. R. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.02.141 · Cited by 922 · see citing works
Engelman, J. A., & Janne, P. A. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-2248 · Cited by 706 · see citing works
Signaling networks assembled by oncogenic EGFR and c-Met
Guo, A., Villén, J., Kornhauser, J. M., Lee, K. A., Stokes, M. P., Rikova, K., Possemato, A. P., Nardone, J., Innocenti, G., Wetzel, R. K., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707270105 · Cited by 502 · see citing works
She, Q., Solit, D. B., Ye, Q., O'Reilly, K. E., Lobo, J. M., & Rosen, N. X. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.09.006 · Cited by 416 · see citing works
McDermott, U., Sharma, S. V., Dowell, L., Greninger, P., Montagut, C. O., Lamb, J. A., Archibald, H., Raudales, R., Tam, A., Lee, D. W., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707498104 · Cited by 356 · see citing works
Gong, Y., Somwar, R., Politi, K. A., Balak, M. N., Chmielecki, J., Jiang, X., & Pao, W. J. (2007) · PLoS Medicine · doi:10.1371/journal.pmed.0040294 · Cited by 322 · see citing works
The tumor-suppressor activity of PTEN is regulated by its carboxyl-terminal region
Georgescu, M.-M., Kirsch, K. H., Akagi, T., Shishido, T., & Hanafusa, H. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.18.10182 · Cited by 318 · see citing works
Mehrian‐Shai, R., Chen, C. D., Shi, T., Horvath, S., Nelson, S. F., Reichardt, J. K. V., & Sawyers, C. L. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0609139104 · Cited by 223 · see citing works
Deng, J., Shimamura, T., Perera, S. A., Carlson, N. E., Cai, D. D., Shapiro, G. I., Wong, K., & Letai, A. G. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-1961 · Cited by 158 · see citing works
Yamasaki, F., Johansen, M. J., Zhang, D., Krishnamurthy, S., Felix, E. A., Bartholomeusz, C., Aguilar, R. J., Kurisu, K., Mills, G. B., Hortobágyi, G. N., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-3020 · Cited by 119 · see citing works
“Oncogenic Shock”: Explaining Oncogene Addiction through Differential Signal Attenuation
Sharma, S. V., Fischbach, M. A., Haber, D. A., & Settleman, J. E. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-0096 · Cited by 117 · see citing works
Toulany, M., Baumann, M. A., & Rodemann, H. P. (2007) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-06-0297 · Cited by 109 · see citing works
Endoh, H., Yatabe, Y., Kosaka, T., Kuwano, H., & Mitsudomi, T. (2006) · Journal of Thoracic Oncology · doi:10.1016/s1556-0864(15)30374-9 · Cited by 82 · see citing works
Endoh, H., Yatabe, Y., Kosaka, T., et al. (2006) · Journal of Thoracic Oncology · doi:10.1097/01243894-200609000-00006 · Cited by 40 · see citing works
Thomas, R. K., Greulich, H. E., Yuza, Y., LEE, J. C., Tengs, T., Feng, W. W., CHEN, T.-H., Nickerson, E., SIMONS, J., EGHOLM, M., et al. (2005) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2005.70.056 · Cited by 38 · see citing works
Sos, M. L., Zander, T., Thomas, R. K., Staratschek‐Jox, A., Claasen, J., & Wolf, J. (2008) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e3181622c05 · Cited by 14 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Cross, D. A. E., Ashton, S. E., Ghiorghiu, S., Eberlein, C., Nebhan, C. A., Spitzler, P. J., Orme, J. P., Finlay, M. R. V., Ward, R. A., Mellor, M. J., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-0337 · Cited by 2,246 · see citing works
Self-citationBrastianos, P. K., Carter, S. L., Santagata, S., Cahill, D. P., Taylor-Weiner, A. N., Jones, R. T., Allen, E. M. V., Lawrence, M. S., Horowitz, P. M., Cibulskis, K., et al. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-0369 · Cited by 1,084 · see citing works
Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer
Pao, W., & Chmielecki, J. (2010) · Nature Reviews Cancer · doi:10.1038/nrc2947 · Cited by 1,083 · see citing works
Kinase drug discovery 20 years after imatinib: progress and future directions
Cohen, P., Cross, D. A. E., & Janne, P. A. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00195-4 · Cited by 1,066 · 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 · see citing works
ERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics
Arteaga, C. L., & Engelman, J. A. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.02.025 · Cited by 1,048 · see citing works
Understanding and targeting resistance mechanisms in NSCLC
Rotow, J. K., & Bivona, T. G. (2017) · Nature reviews. Cancer · doi:10.1038/nrc.2017.84 · Cited by 978 · see citing works
PTEN loss in the continuum of common cancers, rare syndromes and mouse models
Hollander, M. C., Blumenthal, G. M., & Dennis, P. A. (2011) · Nature reviews. Cancer · doi:10.1038/nrc3037 · Cited by 793 · see citing works
Attacking the PI3K/Akt/mTOR signaling pathway for targeted therapeutic treatment in human cancer
Yu, L., Wei, J., & Liu, P. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.06.019 · Cited by 785 · see citing works
Mechanisms of acquired resistance to first- and second-generation EGFR tyrosine kinase inhibitors
Westover, D., Zugazagoitia, J., Cho, B. C., Lovly, C. M., & Paz-Ares, L. (2018) · Annals of Oncology · doi:10.1093/annonc/mdx703 · Cited by 766 · see citing works
Mechanisms of resistance to EGFR tyrosine kinase inhibitors
Huang, L., & Fu, L. (2015) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2015.07.001 · Cited by 596 · see citing works
Overcoming therapy resistance in EGFR-mutant lung cancer
Passaro, A., Jänne, P. A., Mok, T., & Peters, S. (2021) · Nature Cancer · doi:10.1038/s43018-021-00195-8 · Cited by 565 · see citing works
Drug resistance via feedback activation of Stat3 in oncogene-addicted cancer cells
Lee, H.-J., Zhuang, G., Cao, Y., Du, P., Kim, H.-J., & Settleman, J. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.05.019 · Cited by 555 · see citing works
A 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
Overcoming acquired resistance to anticancer therapy: focus on the PI3K/AKT/mTOR pathway
Burris, H. A. (2013) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-012-2043-3 · Cited by 446 · see citing works
EGFR-TKIs resistance via EGFR-independent signaling pathways
Liu, Q., Yu, S., Zhao, W., Qin, S., Chu, Q., & Wu, K. (2018) · Molecular Cancer · doi:10.1186/s12943-018-0793-1 · Cited by 413 · see citing works
FAS and NF-κB signalling modulate dependence of lung cancers on mutant EGFR
Bivona, T. G., Hieronymus, H., Parker, J., Chang, K., Taron, M., Rosell, R., Moonsamy, P., Dahlman, K., Miller, V. A., Costa, C., et al. (2011) · Nature · doi:10.1038/nature09870 · Cited by 396 · see citing works
Treatment approaches for EGFR-inhibitor-resistant patients with non-small-cell lung cancer
Tan, C., Gilligan, D., & Pacey, S. (2015) · The Lancet Oncology · doi:10.1016/s1470-2045(15)00246-6 · Cited by 390 · see citing works
Garofalo, M., Romano, G., Leva, G. D., Nuovo, G. J., Jeon, Y.-J., Ngankeu, A., Sun, J., Lovat, F., Alder, H., Condorelli, G., et al. (2011) · Nature Medicine · doi:10.1038/nm.2577 · Cited by 368 · see citing works
RetractedA perspective on anti-EGFR therapies targeting triple-negative breast cancer.
Nakai, K., Hung, M., & Yamaguchi, H. (2016) · Europe PMC (PubMed Central) · Cited by 324 · see citing works
Overcoming resistance to tumor-targeted and immune-targeted therapies
Aldea, M., Andre, F., Marabelle, A., Dogan, S., Barlesi, F., & Soria, J.-C. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-1638 · Cited by 311 · see citing works
Stewart, E., Tan, S. Z., Liu, G., & Tsao, M. (2015) · Europe PMC (PubMed Central) · doi:10.3978/j.issn.2218-6751.2014.11.06 · Cited by 311 · see citing works
Lim, S. M., Syn, N. L. X., Cho, B. C., & Soo, R. A. (2018) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2018.02.006 · Cited by 289 · see citing works
Antitumour immunity regulated by aberrant ERBB family signalling
Kumagai, S., Koyama, S., & Nishikawa, H. (2021) · Nature reviews. Cancer · doi:10.1038/s41568-020-00322-0 · Cited by 279 · see citing works
Suda, K., Tomizawa, K., Fujii, M., Murakami, H., Osada, H., Maehara, Y., Yatabe, Y., Sekido, Y., & Mitsudomi, T. (2011) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e318216ee52 · Cited by 277 · see citing works
PTEN Loss Mediates Clinical Cross-Resistance to CDK4/6 and PI3Kα Inhibitors in Breast Cancer
Costa, C., Wang, Y., Ly, A., Hosono, Y., Murchie, E., Walmsley, C. S., Huynh, T. G., Healy, C., Peterson, R., Yanase, S., et al. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-0830 · Cited by 272 · see citing works
Chen, G., Umelo, I. A., Lv, S., Teugels, E., Fostier, K., Kronenberger, P., Dewaele, A., Sadones, J., Geers, C., & Grève, J. D. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060317 · Cited by 265 · see citing works
Differential Protein Stability and ALK Inhibitor Sensitivity of EML4-ALK Fusion Variants
Heuckmann, J. M., Balke‐Want, H., Malchers, F., Peifer, M., Sos, M. L., Koker, M., Meder, L., Lovly, C. M., Heukamp, L. C., Pao, W. J., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-3260 · Cited by 261 · see citing works
Sos, M. L., Fischer, S., Ullrich, R. T., Peifer, M., Heuckmann, J. M., Koker, M., Heynck, S., Stückrath, I., Weiss, J. M., Fischer, F., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0907325106 · Cited by 255 · see citing works
Nagano, T., TACHIHARA, M. Y., & Nishimura, Y. (2018) · Cells · doi:10.3390/cells7110212 · Cited by 252 · see citing works
Targeted therapy in non-small-cell lung cancer—is it becoming a reality?
Jankú, F., Stewart, D. J., & Kurzrock, R. (2010) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2010.64 · Cited by 252 · see citing works
Molecular pathology of lung cancer: key to personalized medicine
Liang Cheng, C., Alexander, R. E., MacLennan, G. T., Cummings, O. W., Montironi, R., Antonio Lopez-beltran, B., Cramer, H. M., Davidson, D. D., & Zhang, S. (2012) · Modern Pathology · doi:10.1038/modpathol.2011.215 · Cited by 245 · see citing works
PTEN and PI3K/AKT in Non-Small-Cell Lung Cancer
Pérez-Ramírez, C., Cañadas‐Garre, M., Molina‐Vila, M. Á., Faus-Dáder, M. J., & Calleja‐Hernández, M. Á. (2015) · Pharmacogenomics · doi:10.2217/pgs.15.122 · Cited by 238 · see citing works
Epidermal growth factor receptor mutations in lung adenocarcinoma
Siegelin, M. D., & Borczuk, A. (2013) · Laboratory Investigation · doi:10.1038/labinvest.2013.147 · Cited by 233 · see citing works
Thunnissen, E., Kerr, K. M., Herth, F. J. F., Lantuéjoul, S., Papotti, M. G., Rintoul, R. C., Rossi, G., Skov, B. G., Weynand, B., Bubendorf, L., et al. (2011) · Lung Cancer · doi:10.1016/j.lungcan.2011.10.017 · Cited by 228 · see citing works
Mechanisms of Acquired Resistance to AZD9291
Kim, T. M., Song, A., Kim, D., Kim, S., Ahn, Y., Keam, B., Jeon, Y. K., Lee, S., Chung, D. H., & Heo, D. S. (2015) · Journal of Thoracic Oncology · doi:10.1097/jto.0000000000000688 · Cited by 225 · see citing works
Sos, 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 · see citing works
Drug resistance to targeted therapeutic strategies in non-small cell lung cancer
Liu, W., Du, Y., Wen, R. M., Yang, M., & Xu, J. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.107438 · Cited by 218 · see citing works
Wang, Z., Cheng, Y., An, T., Gao, H., Wang, K., Zhou, Q. H., Hu, Y., Song, Y., Ding, C., Peng, F., et al. (2018) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(18)30264-9 · Cited by 217 · see citing works
Selective targeting of radiation-resistant tumor-initiating cells
Zhang, M., Atkinson, R. L., & Rosen, J. M. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910179107 · Cited by 216 · see citing works
Combined EGFR/MEK Inhibition Prevents the Emergence of Resistance in EGFR -Mutant Lung Cancer
Tricker, E. M., Xu, C., Uddin, S., Capelletti, M., Ercan, D., Ogino, A., Pratilas, C. A., Rosen, N. X., Gray, N. S., Wong, K., et al. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-0063 · Cited by 207 · see citing works
O'Byrne, K. J., Gatzemeier, U., Bondarenko, I., Barrios, C. H., Eschbach, C., Martens, U. M., Hotko, Y., Kortsik, C., Paz-Ares, L. G., Pereira, J. R., et al. (2011) · The Lancet Oncology · doi:10.1016/s1470-2045(11)70189-9 · Cited by 205 · see citing works
Reduced 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
Sanaei, M., Razi, S., Pourbagheri‐Sigaroodi, A., & Bashash, D. (2022) · Translational Oncology · doi:10.1016/j.tranon.2022.101364 · Cited by 204 · see citing works
EGFR-TKI resistance in NSCLC patients: mechanisms and strategies.
Lin, Y., Wang, X., & Jin, H. (2014) · Europe PMC (PubMed Central) · Cited by 198 · see citing works
mTOR signaling in glioblastoma: lessons learned from bench to bedside
Akhavan, D., Cloughesy, T. F., & Mischel, P. S. (2010) · Neuro-Oncology · doi:10.1093/neuonc/noq052 · Cited by 190 · see citing works
ALK Mutations Conferring Differential Resistance to Structurally Diverse ALK Inhibitors
Heuckmann, J. M., Hölzel, M., Sos, M. L., Heynck, S., Balke‐Want, H., Koker, M., Peifer, M., Weiss, J. M., Lovly, C. M., Grütter, C., et al. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-1648 · Cited by 192 · see citing works
Minari, R., Bordi, P., & Tiseo, M. (2016) · Translational Lung Cancer Research · doi:10.21037/tlcr.2016.12.02 · Cited by 186 · see citing works
PTEN Tumor-Suppressor: The Dam of Stemness in Cancer
Luongo, F., Colonna, F., Calapà, F., Vitale, S., Fiori, M. E., & Maria, R. D. (2019) · Cancers · doi:10.3390/cancers11081076 · Cited by 192 · see citing works
Bhatia, P., Sharma, V., Alam, O., Manaithiya, A., Alam, P., Kahksha, Alam, M. T., & Imran, M. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112640 · Cited by 183 · 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 · see citing works
Yochum, Z. A., Cades, J., Wang, H., Chatterjee, S., Simons, B. W., O’Brien, J. P., Khetarpal, S. K., Lemtiri-Chlieh, G., Myers, K. V., Huang, E. H. ‐., et al. (2018) · Oncogene · doi:10.1038/s41388-018-0482-y · Cited by 178 · see citing works
Li, B., Ren, S., Li, X., Wang, Y., Garfield, D. H., Zhou, S., Chen, X., Su, C., Chen, M., Kuang, P., et al. (2013) · Lung Cancer · doi:10.1016/j.lungcan.2013.11.003 · Cited by 176 · see citing works
Nukaga, S., Yasuda, H., Tsuchihara, K., Hamamoto, J., Masuzawa, K., Kawada, I., Naoki, K., Matsumoto, S., Mimaki, S., Ikemura, S., et al. (2017) · Cancer Research · doi:10.1158/0008-5472.can-16-2359 · Cited by 179 · see citing works
Su, Z., Dias-Santagata, D., Duke, M., Hutchinson, K., Lin, Y.-L., Borger, D. R., Chung, C. H., Massion, P. P., Vnencak-Jones, C. L., Iafrate, A. J., et al. (2011) · The Journal of Molecular Diagnostics · doi:10.1016/j.jmoldx.2010.11.010 · Cited by 176 · see citing works
Modjtahedi, H., & Essapen, S. (2009) · Anti-Cancer Drugs · doi:10.1097/cad.0b013e3283330590 · Cited by 175 · see citing works
Ekert, J. E., Johnson, K., Strake, B., Pardinas, J. R., Jarantow, S. W., Perkinson, R. A., & Colter, D. C. (2014) · PLoS ONE · doi:10.1371/journal.pone.0092248 · Cited by 165 · see citing works
Mechanisms of Acquired Resistance to Targeted Cancer Therapies
Lackner, M. R., Wilson, T. R., & Settleman, J. (2012) · Future Oncology · doi:10.2217/fon.12.86 · Cited by 163 · see citing works
Molecular mechanisms of resistance in epidermal growth factor receptor-mutant lung adenocarcinomas
Cortot, A. B., & Jänne, P. A. (2014) · European Respiratory Review · doi:10.1183/09059180.00004614 · Cited by 158 · see citing works
Yamamoto, C., Basaki, Y., Kawahara, A., Nakashima, K., Kage, M., Izumi, H., Kohno, K., Uramoto, H., Yasumoto, K., Kuwano, M., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-0043 · Cited by 155 · see citing works
Personalized therapy for lung cancer: striking a moving target
Pakkala, S., & Ramalingam, S. S. (2018) · JCI Insight · doi:10.1172/jci.insight.120858 · Cited by 149 · see citing works
The multiple facets of drug resistance: one history, different approaches
Niero, E. L. D. O., Rocha-Sales, B., Lauand, C., Cortez, B. A., de Souza, M. M., Teixeira, P. R., Urabayashi, M. S., Martens, A. A., Neves, J. H., & Machado‐Santelli, G. M. (2014) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/1756-9966-33-37 · Cited by 135 · see citing works
Chen, G., Kronenberger, P., Teugels, E., Umelo, I. A., & Grève, J. D. (2012) · BMC Medicine · doi:10.1186/1741-7015-10-28 · Cited by 132 · see citing works
Lee, J. J.-K., Shin, J. Y., Kim, S., Lee, S., Park, C. C., Kim, J. Y., Koh, Y., Keam, B., Min, H. S., Kim, T. M., et al. (2013) · Annals of Oncology · doi:10.1093/annonc/mdt127 · Cited by 128 · see citing works
Yoon, Y., Kim, H., Han, S., Oh, D. Y., Im, S., Bang, Y., & Kim, T. (2010) · Molecular Carcinogenesis · doi:10.1002/mc.20607 · Cited by 129 · see citing works
Emerging roles of radioresistance in prostate cancer metastasis and radiation therapy
Chang, L., Graham, P., Hao, J., Bucci, J. A., Cozzi, P. J., Kearsley, J. H., & Li, Y. (2014) · Cancer and Metastasis Reviews · doi:10.1007/s10555-014-9493-5 · Cited by 124 · see citing works
Hensing, T. A., Chawla, A., Batra, R., & Salgia, R. (2013) · Advances in experimental medicine and biology · doi:10.1007/978-1-4614-8778-4_5 · Cited by 125 · see citing works
EGFR Blockade Enriches for Lung Cancer Stem–like Cells through Notch3-Dependent Signaling
Arasada, R. R., Amann, J. M., Rahman, M. A., Huppert, S. S., & Carbone, D. P. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-3724 · Cited by 124 · see citing works
Cheng, Y., Zhang, T., & Xu, Q. (2021) · MedComm · doi:10.1002/mco2.105 · Cited by 125 · see citing works
Drug resistance in lung cancer
Ramesh, R. (2010) · Lung Cancer Targets and Therapy · doi:10.2147/lctt.s6861 · Cited by 123 · see citing works
Jia, Y., Juarez, J., Li, J., Manuia, M., Niederst, M. J., Tompkins, C., Timple, N., Vaillancourt, M.-T., Pferdekamper, A. C., Lockerman, E. L., et al. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-2581 · Cited by 121 · see citing works
Buettner, R., Wolf, J., & Thomas, R. K. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.45.9867 · Cited by 121 · see citing works
DUSP1/MKP1 promotes angiogenesis, invasion and metastasis in non-small-cell lung cancer
Moncho-Amor, V., de Cáceres, I. I., Bandrés, E., Martı́nez-Poveda, B., Orgaz, J. L., Sánchez‐Pérez, I., Zazo, S., Rovira, A., Albanell, J., Jiménez, B., et al. (2010) · Oncogene · doi:10.1038/onc.2010.449 · Cited by 119 · see citing works
Molecular Mechanisms and Targeted Therapies Including Immunotherapy for Non-Small Cell Lung Cancer
Nagano, T., TACHIHARA, M. Y., & Nishimura, Y. (2018) · Current Cancer Drug Targets · doi:10.2174/1568009619666181210114559 · Cited by 118 · see citing works
Shalaby, A. A., Presneau, N., Ye, H., Halai, D., Berisha, F., Idowu, B. D., Leithner, A., Liegl, B., Briggs, T. W. R., Bácsi, K., et al. (2010) · The Journal of Pathology · doi:10.1002/path.2818 · Cited by 118 · see citing works
Cho, J., Chen, L., Sangji, N., Okabe, T., Yonesaka, K., Francis, J. M., Flavin, R. J., Johnson, W., Kwon, J., Yu, S., et al. (2013) · Cancer Research · doi:10.1158/0008-5472.can-13-1145 · Cited by 117 · see citing works
Self-citationDirectly targeting transcriptional dysregulation in cancer
Gonda, T. J., & Ramsay, R. G. (2015) · Nature reviews. Cancer · doi:10.1038/nrc4018 · Cited by 119 · see citing works
Chen, L. F., Cohen, E. E. W., & Grandis, J. R. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-2318 · Cited by 117 · see citing works
Wang, Y.-S., Wang, Y., Xia, H., Zhou, S., Schmid‐Bindert, G., & Zhou, C. (2012) · Asian Pacific Journal of Cancer Prevention · doi:10.7314/apjcp.2012.13.1.255 · Cited by 114 · see citing works
Gadgeel, S. M., & Wozniak, A. J. (2013) · Clinical Lung Cancer · doi:10.1016/j.cllc.2012.12.001 · Cited by 114 · see citing works
EGFR mutations and the terminal respiratory unit
Yatabe, Y. (2010) · Cancer and Metastasis Reviews · doi:10.1007/s10555-010-9205-8 · Cited by 112 · see citing works
Modjtahedi, H., Cho, B. C., Michel, M. C., & Solca, F. (2014) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-014-0967-3 · Cited by 109 · see citing works
PTEN in Lung Cancer: Dealing with the Problem, Building on New Knowledge and Turning the Game Around
Γκουντάκος, Α., Sartori, G., Falcone, I., Piro, G., Ciuffreda, L., Carbone, C., Tortora, G., Scarpa, A., Bria, E., Milella, M., et al. (2019) · Cancers · doi:10.3390/cancers11081141 · Cited by 106 · see citing works
Lung cancer in never smokers: Change of a mindset in the molecular era
Lee, Y. J., Kim, J.-H., Kim, S. I., Ha, S., Mok, T. S. K., Mitsudomi, T., & Cho, B. C. (2011) · Lung Cancer · doi:10.1016/j.lungcan.2010.12.013 · Cited by 105 · see citing works
Targeting the Akt Kinase to Modulate Survival, Invasiveness and Drug Resistance of Cancer Cells
Cassinelli, G., Zuco, V., Gatti, L., Lanzi, C., Zaffaroni, N., Colombo, D., & Perego, P. (2013) · Current Medicinal Chemistry · doi:10.2174/09298673113209990106 · Cited by 103 · see citing works
The next tier of EGFR resistance mutations in lung cancer
Tumbrink, H. L., Heimsoeth, A., & Sos, M. L. (2020) · Oncogene · doi:10.1038/s41388-020-01510-w · Cited by 101 · see citing works
Targeted therapy for triple‐negative breast cancer: Where are we?
Duffy, M. J., McGowan, P. M., & Crown, J. P. (2012) · International Journal of Cancer · doi:10.1002/ijc.27632 · Cited by 102 · see citing works
Selective Antitumor Activity of Ibrutinib in EGFR-Mutant Non–Small Cell Lung Cancer Cells
Gao, W., Wang, M. L., Wang, L., Lu, H., Wu, S., Dai, B., Ou, Z., Zhang, L., Heymach, J. V., Gold, K. A., et al. (2014) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/dju204 · Cited by 99 · see citing works
Resistance is futile: overcoming resistance to targeted therapies in lung adenocarcinoma
Neel, D. S., & Bivona, T. G. (2017) · npj Precision Oncology · doi:10.1038/s41698-017-0007-0 · Cited by 98 · see citing works
The evolving genomic classification of lung cancer
Shames, D. S., & Wistuba, I. I. (2013) · The Journal of Pathology · doi:10.1002/path.4275 · Cited by 98 · see citing works
Rao, G., Pierobon, M., Kim, I., Hsu, W., Deng, J., Moon, Y., Petricoin, E. F., Zhang, Y., Wang, Y., & Giaccone, G. (2017) · Scientific Reports · doi:10.1038/s41598-017-06128-9 · Cited by 98 · see citing works
Lee, S. Y., Kim, M. J., Jin, G., Yoo, S. S., Park, J. Y., Choi, J. E., Jeon, H. S., Cho, S., Lee, E. B., Cha, S. I., et al. (2010) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e3181f0beca · Cited by 97 · see citing works
Yoshida, T., Song, L., Bai, Y., Kinose, F., Li, J., Ohaegbulam, K. C., Muñoz-Antonia, T., Qu, X., Eschrich, S. A., Uramoto, H., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0147344 · Cited by 96 · see citing works
Phase II Trial of Gefitinib and Everolimus in Advanced Non-small Cell Lung Cancer
Price, K. A. R., Azzoli, C. G., Krug, L. M., Pietanza, M. C., Rizvi, N. A., Pao, W. J., Kris, M. G., Riely, G. J., Heelan, R. T., Arcila, M. E., et al. (2010) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e3181ec1531 · Cited by 93 · see citing works
Zhang, Y., Zeng, Y., Liu, T., Du, W., Zhu, J., Liu, Z., & Huang, J. (2019) · Respiratory Research · doi:10.1186/s12931-019-1137-4 · Cited by 93 · see citing works
Jamme, P., Fernandes, M., Copin, M., Descarpentries, C., Escande, F., Morabito, A., Grégoire, V., Jamme, M., Baldacci, S., Tulasne, D., et al. (2020) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2020.01.027 · Cited by 91 · see citing works
Drug Resistance to EGFR Inhibitors in Lung Cancer
Tetsu, O., Hangauer, M. J., Phuchareon, J., Eisele, D. W., & McCormick, F. P. (2016) · Chemotherapy · doi:10.1159/000443368 · Cited by 88 · see citing works
Gilmour, A. M., Abdulkhalek, S., Cheng, T. S. W., Alghamdi, F., Jayanth, P., O'Shea, L., Geen, O. D., Arvizu, L. A., & Szewczuk, M. R. (2013) · Cellular Signalling · doi:10.1016/j.cellsig.2013.08.008 · Cited by 90 · see citing works
Targeting epidermal growth factor receptor: Central signaling kinase in lung cancer
Yoshida, T., Zhang, G., & Haura, E. B. (2010) · Biochemical Pharmacology · doi:10.1016/j.bcp.2010.05.014 · Cited by 89 · see citing works
Prognostic significance of epithelial–mesenchymal transition in malignant pleural mesothelioma☆☆☆
Schramm, A., Opitz, I., Thies, S., Seifert, B., Moch, H., Weder, W., & Soltermann, A. (2009) · European Journal of Cardio-Thoracic Surgery · doi:10.1016/j.ejcts.2009.08.027 · Cited by 89 · see citing works
- Authors
- Sos, M. L., Koker, M., Weir, B. A., Heynck, S., Rabinovsky, R., Zander, T., Seeger, J. M., Weiss, J., Fischer, F., Frommolt, P., Michel, K., Peifer, M., Mermel, C., Girard, L., Peyton, M., Gazdar, A. F., Minna, J. D., Garraway, L. A., Kashkar, H., Pao, W., Meyerson, M., & Thomas, R. K.
- Affiliations
- Max Planck Society (DE)
- Broad Institute (US)
- Harvard University (US)
- University of Cologne (DE)
- The University of Texas Southwestern Medical Center (US)
- Memorial Sloan Kettering Cancer Center (US)
- ORCID
- Venue
- Cancer Research
- Published
- 2009-04-15
- Volume
- 69
- Issue
- 8
- Pages
- 3256-3261
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- PMC
- PMC2849653
- OpenAlex
- W2133488997
- Cited by
- 504
- References
- 21
- Citations by year
- 2026: 8 · 2025: 15 · 2024: 15 · 2023: 20 · 2022: 17 · 2021: 25 · 2020: 30 · 2019: 31 · 2018: 39 · 2017: 33 · 2016: 34 · 2015: 45 · 2014: 35 · 2013: 48 · 2012: 31
- FWCI
- 30.59
- Type
- journal article
- Language
- en
- Update notices
- correction (2025-03-03)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- National Cancer Institute (R01CA116020, (P50-CA70907, P50CA070907)
- National Institute of General Medical Sciences (T32GM007753)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- PTEN loss, erlotinib resistance, EGFR-mutant lung cancer, non-small cell lung cancer, Akt signaling, EGFR activation, EGFR inhibition, T790M mutation, MET amplification
- MeSH terms
- Erlotinib Hydrochloride, Carcinoma, Non-Small-Cell Lung, Chromosome Aberrations, Enzyme Activation, Humans, Lung Neoplasms, Quinazolines, Gene Expression, Cluster Analysis, Gene Deletion, Drug Resistance, Neoplasm, Cell Line, Tumor, Protein Kinase Inhibitors, Proto-Oncogene Proteins c-akt, PTEN Phosphohydrolase, ErbB Receptors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
