FAS and NF-κB signalling modulate dependence of lung cancers on mutant EGFR
Open accessAbstract
Human lung adenocarcinomas with activating mutations in EGFR (epidermal growth factor receptor) often respond to treatment with EGFR tyrosine kinase inhibitors (TKIs), but the magnitude of tumour regression is variable and transient. This heterogeneity in treatment response could result from genetic modifiers that regulate the degree to which tumour cells are dependent on mutant EGFR. Through a pooled RNA interference screen, we show that knockdown of FAS and several components of the NF-κB pathway specifically enhanced cell death induced by the EGFR TKI erlotinib in EGFR-mutant lung cancer cells. Activation of NF-κB through overexpression of c-FLIP or IKK (also known as CFLAR and IKBKB, respectively), or silencing of IκB (also known as NFKBIA), rescued EGFR-mutant lung cancer cells from EGFR TKI treatment. Genetic or pharmacologic inhibition of NF-κB enhanced erlotinib-induced apoptosis in erlotinib-sensitive and erlotinib-resistant EGFR-mutant lung cancer models. Increased expression of the NF-κB inhibitor IκB predicted for improved response and survival in EGFR-mutant lung cancer patients treated with EGFR TKI. These data identify NF-κB as a potential companion drug target, together with EGFR, in EGFR-mutant lung cancers and provide insight into the mechanisms by which tumour cells escape from oncogene dependence.
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In erlotinib-sensitive and erlotinib-resistant EGFR-mutant lung cancer models, genetic or pharmacologic inhibition of NF-κB increased erlotinib-induced apoptosis.
“In erlotinib-sensitive and erlotinib-resistant EGFR-mutant lung cancer models, genetic or pharmacologic inhibition of NF-κB increased erlotinib-induced apoptosis [114].”
From Emerging Insights into Targeted Therapy-Tolerant Persister Cells in Cancer (2021) · cites this paper as [114]
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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
Self-citationScreening for Epidermal Growth Factor Receptor Mutations in Lung Cancer
Rosell, R., Moran, T., Queralt, C., Porta, R., Cardenal, F., Camps, C., Majem, M., Lopez-Vivanco, G., Isla, D., Provencio, M., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0904554 · Cited by 2,373 · see citing works
Self-citationMelanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation
Nazarian, R., Shi, H., Wang, Q., Kong, X., Koya, R. C., Lee, H., Chen, Z., Lee, M., Attar, N., Sazegar, H., et al. (2010) · Nature · doi:10.1038/nature09626 · Cited by 2,198 · 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-citationCOT drives resistance to RAF inhibition through MAP kinase pathway reactivation
Johannessen, C. M., Boehm, J. S., Kim, S. Y., Thomas, S. R., Wardwell, L., Johnson, L. A., Emery, C. M., Stransky, N., Cogdill, A. P., Barretina, J., et al. (2010) · Nature · doi:10.1038/nature09627 · Cited by 1,460 · see citing works
Self-citationPreexistence 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
IKK/NF- B signaling: balancing life and death - a new approach to cancer therapy
Luo, J. (2005) · Journal of Clinical Investigation · doi:10.1172/jci26322 · Cited by 879 · see citing works
Weinstein, I. B., & Joe, A. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-3293 · Cited by 805 · see citing works
Targeting the cancer kinome through polypharmacology
Knight, Z. A., Lin, H., & Shokat, K. M. (2010) · Nature reviews. Cancer · doi:10.1038/nrc2787 · Cited by 674 · see citing works
Requirement for NF-κB signalling in a mouse model of lung adenocarcinoma
Meylan, E., Dooley, A. L., Feldser, D. M., Shen, L., Turk, E., Ouyang, C., & Jacks, T. (2009) · Nature · doi:10.1038/nature08462 · Cited by 514 · see citing works
Sos, M. L., Koker, M., Weir, B. A., Heynck, S., Rabinovsky, R., Zander, T., Seeger, J. M., Weiss, J., Fischer, F., Frommolt, P., et al. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-4055 · Cited by 504 · see citing works
Engelman, J. A., Mukohara, T., Zejnullahu, K., Lifshits, E., Borras, A. M., Gale, C.-M., Naumov, G. N., Yeap, B. Y., Jarrell, E., Sun, J., et al. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28656 · Cited by 457 · see citing works
Membrane-bound Fas ligand only is essential for Fas-induced apoptosis
O’ Reilly, L. A., Tai, L., Lee, L., Kruse, E. A., Grabow, S., Fairlie, W. D., Haynes, N. M., Tarlinton, D. M., Zhang, J.-G., Belz, G. T., et al. (2009) · Nature · doi:10.1038/nature08402 · Cited by 400 · see citing works
The CD95 Receptor: Apoptosis Revisited
Peter, M. E., Budd, R. C., Desbarats, J., Hedrick, S. Μ., Hueber, A., Newell, M. K., Owen, L. B., Pope, R. M., Tschopp, J. F., Wajant, H., et al. (2007) · Cell · doi:10.1016/j.cell.2007.04.031 · Cited by 396 · see citing works
Chen, L., Park, S.-M., Tumanov, A. V., Hau, A., Sawada, K., Feig, C., Turner, J. R., Fu, Y., Romero, I. L., Lengyel, E. R., et al. (2010) · Nature · doi:10.1038/nature09075 · Cited by 377 · see citing works
Profiling Essential Genes in Human Mammary Cells by Multiplex RNAi Screening
Silva, J. M., Marran, K., Parker, J. S., Silva, J., Golding, M. C., Schlabach, M. R., Elledge, S. J., Hannon, G. J., & Chang, K. (2008) · Science · doi:10.1126/science.1149185 · Cited by 317 · see citing works
Self-citationMiller, V. A., Riely, G. J., Zakowski, M. F., Li, A. R., Patel, J. D., Heelan, R. T., Kris, M. G., Sandler, A. B., Carbone, D. P., Tsao, A. S., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.13.0062 · Cited by 295 · see citing works
Self-citationSato, M., Vaughan, M. B., Girard, L., Peyton, M., Lee, W., Shames, D. S., Ramirez, R. D., Sunaga, N., Gazdar, A. F., Shay, J. W., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-2521 · Cited by 260 · see citing works
An integrated genomic analysis of lung cancer reveals loss of DUSP4 in EGFR-mutant tumors
Chitale, D. A., Gong, Y., Taylor, B. S., Broderick, S., Brennan, C. W., Somwar, R., Golas, B., Wang, L., Motoi, N., Szőke, J., et al. (2009) · Oncogene · doi:10.1038/onc.2009.135 · Cited by 230 · see citing works
Yang, J., Amiri, K. I., Burke, J. R., Schmid, J. A., & Richmond, A. J. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-1220 · Cited by 167 · see citing works
Gong, Y., Yao, E. S., Shen, R., Goel, A. J., Arcila, M. E., Teruya‐Feldstein, J., Zakowski, M. F., Frankel, S., Peifer, M., Thomas, R. K., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007273 · Cited by 128 · see citing works
Molecular Targeted Therapy of Lung Cancer: EGFR Mutations and Response to EGFR InhibitorsPreprint
Haber, D. A., Bell, D. W., Sordella, R., Kwak, E. L., Godin-Heymann, N., Sharma, S. V., Lynch, T. J., & Settleman, J. E. (2005) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2005.70.043 · Cited by 116 · see citing works
Green, D. R. (2010) · Nature · doi:10.1038/465433a · Cited by 11 · see citing works
Flagged first, then by citations
1 of the 24 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
NF-κB, inflammation, immunity and cancer: coming of age
Taniguchi, K., & Karin, M. (2018) · Nature Reviews Immunology · doi:10.1038/nri.2017.142 · Cited by 2,679 · see citing works
Non-small-cell lung cancers: a heterogeneous set of diseases
Chen, Z., Brainson, C. F., Hammerman, P. S., Kim, C. F., & Wong, K. (2014) · Nature reviews. Cancer · doi:10.1038/nrc3775 · Cited by 1,935 · see citing works
Inflammation meets cancer, with NF-κB as the matchmaker
Ben‐Neriah, Y., & Karin, M. (2011) · Nature Immunology · doi:10.1038/ni.2060 · Cited by 1,378 · see citing works
Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer
Zhang, Z., Lee, J. C., Lin, L., Olivas, V., Au, V., LaFramboise, T., Abdel-Rahman, M., Wang, X., Levine, A. D., Rho, J. K., et al. (2012) · Nature Genetics · doi:10.1038/ng.2330 · Cited by 1,224 · see citing works
Self-citationThe 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
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
Self-citationCell death-based treatment of lung adenocarcinoma
Denisenko, T. V., Budkevich, I. N., & Zhivotovsky, B. (2018) · Cell Death & Disease · doi:10.1038/s41419-017-0063-y · Cited by 768 · see citing works
Evolutionary dynamics of cancer in response to targeted combination therapy
Božić, I., Reiter, J. G., Allen, B., Tibor Antal, A., Chatterjee, K., Shah, P., Moon, Y. S., Yaqubie, A., Kelly, N. E., Le, D. T., et al. (2013) · eLife · doi:10.7554/elife.00747 · Cited by 607 · see citing works
Blakely, C. M., Watkins, T. B. K., Wu, W., Gini, B., Chabon, J. J., McCoach, C. E., McGranahan, N., Wilson, G. A., Birkbak, N. J., Olivas, V. R., et al. (2017) · Nature Genetics · doi:10.1038/ng.3990 · Cited by 571 · see citing works
Self-citationNg, K. P., Hillmer, A. M., Chuah, C. T. H., Juan, W. C., Ko, T. K., Teo, A. S. M., Ariyaratne, P. N., Takahashi, N., Sawada, K., Fei, Y., et al. (2012) · Nature Medicine · doi:10.1038/nm.2713 · Cited by 557 · see citing works
The Hippo effector YAP promotes resistance to RAF- and MEK-targeted cancer therapies
Lin, L., Sabnis, A. J., Chan, E., Olivas, V., Cade, L., Pazarentzos, E., Asthana, S., Neel, D., Yan, J. J., Lu, X., et al. (2015) · Nature Genetics · doi:10.1038/ng.3218 · Cited by 551 · see citing works
Self-citationThird-generation EGFR and ALK inhibitors: mechanisms of resistance and management
Cooper, A. J., Sequist, L. V. D., & Lin, J. J. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-022-00639-9 · Cited by 525 · see citing works
Optimization of Dosing for EGFR-Mutant Non–Small Cell Lung Cancer with Evolutionary Cancer Modeling
Chmielecki, J., Foo, J., Oxnard, G. R., Hutchinson, K. E., Ohashi, K., Somwar, R., Wang, L., Amato, K. R., Arcila, M. E., Sos, M. L., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002356 · Cited by 519 · see citing works
Self-citationCircumventing cancer drug resistance in the era of personalized medicine
Garraway, L. A., & Jänne, P. A. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0012 · Cited by 503 · see citing works
The TNF Family of Ligands and Receptors: Communication Modules in the Immune System and Beyond
Dostert, C., Grusdat, M., Letellier, E., & Brenner, D. (2018) · Physiological Reviews · doi:10.1152/physrev.00045.2017 · Cited by 502 · see citing works
Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor–Resistant Disease
Ohashi, K., Maruvka, Y. E., Michor, F., & Pao, W. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.43.3912 · Cited by 467 · 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
An integrin β3-KRAS-RalB complex drives tumour stemness and resistance to EGFR inhibition
Seguin, L., Kato, S., Franovic, A., Camargo, M. F., Lesperance, J., Elliott, K. C., Yebra, M., Mielgo, A., Lowy, A. M., Husain, H., et al. (2014) · Nature Cell Biology · doi:10.1038/ncb2953 · Cited by 374 · see citing works
The role of CD95 and CD95 ligand in cancer
Peter, M. E., Hadji, A., Murmann, A. E., Brockway, S., Putzbach, W., Pattanayak, A., & Ceppi, P. (2015) · Cell Death and Differentiation · doi:10.1038/cdd.2015.3 · Cited by 356 · see citing works
Emerging 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 · see citing works
A 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
Studying the mononuclear phagocyte system in the molecular age
Chow, A. T., Brown, B. D., & Mérad, M. (2011) · Nature reviews. Immunology · doi:10.1038/nri3087 · Cited by 315 · 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
Genetics and biomarkers in personalisation of lung cancer treatment
Rosell, R., Bivona, T. G., & Karachaliou, N. (2013) · The Lancet · doi:10.1016/s0140-6736(13)61715-8 · Cited by 304 · see citing works
Self-citationInflammation-Induced Tumorigenesis and Metastasis
Hibino, S., Kawazoe, T., Kasahara, H., Itoh, S., Ishimoto, T., Sakata‐Yanagimoto, M., & Taniguchi, K. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115421 · Cited by 303 · see citing works
Essential Gene Profiles in Breast, Pancreatic, and Ovarian Cancer Cells
Marcotte, R., Brown, K. R., Suárez, F., Sayad, A., Karamboulas, K., Krzyzanowski, P. M., Sircoulomb, F., Medrano, M., Fedyshyn, Y., Koh, J. L. Y., et al. (2011) · Cancer Discovery · doi:10.1158/2159-8290.cd-11-0224 · Cited by 297 · see citing works
Receptor Tyrosine Kinase-Targeted Cancer Therapy
Yamaoka, T., Kusumoto, S., Ando, K., Ohba, M., & Ohmori, T. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19113491 · Cited by 297 · see citing works
Shah, K. N., Bhatt, R., Rotow, J., Rohrberg, J., Olivas, V., Wang, V. E., Hemmati, G., Martins, M. M., Maynard, A., Kuhn, J., et al. (2019) · Nature Medicine · doi:10.1038/s41591-018-0264-7 · Cited by 286 · see citing works
Self-citationBaldwin, A. S. (2012) · Immunological Reviews · doi:10.1111/j.1600-065x.2012.01095.x · Cited by 277 · see citing works
Oncogenic EGFR Signaling Activates an mTORC2–NF-κB Pathway That Promotes Chemotherapy Resistance
Tanaka, K., Babić, I., Nathanson, D. A., Akhavan, D., Guo, D., Gini, B., Dang, J. H. T., Zhu, S., Yang, H., Jesus, J. D., et al. (2011) · Cancer Discovery · doi:10.1158/2159-8290.cd-11-0124 · Cited by 274 · see citing works
Polytherapy and Targeted Cancer Drug Resistance
Chatterjee, N., & Bivona, T. G. (2019) · Trends in cancer · doi:10.1016/j.trecan.2019.02.003 · Cited by 271 · see citing works
Self-citationJanne, P. A., Wang, X., Socinski, M. A., Crawford, J., Stinchcombe, T. E., Gu, L., Capelletti, M., Edelman, M. J., Villalona-Calero, M. A., Kratzke, R. A., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2011.40.1315 · Cited by 241 · see citing works
Self-citationPersonalized Cancer Medicine: Molecular Diagnostics, Predictive biomarkers, and Drug Resistance
de Castro, D. G., Clarke, P. A., Al‐Lazikani, B., & Workman, P. (2012) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2012.237 · Cited by 234 · see citing works
Resisting Resistance: Targeted Therapies in Lung Cancer
Lin, J. J., & Shaw, A. T. (2016) · Trends in cancer · doi:10.1016/j.trecan.2016.05.010 · Cited by 232 · 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
EGFR and NF-κB: partners in cancer
Shostak, K., & Chariot, A. (2015) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2015.04.001 · Cited by 218 · see citing works
Co-activation of STAT3 and YES-Associated Protein 1 (YAP1) Pathway in EGFR-Mutant NSCLC
CHAIB-OUKADOUR, I., Karachaliou, N., Pilotto, S., Servat, J. C., Cai, X., Li, X., Drozdowskyj, A., Codony, C., Yang, J. E., Hu, C., et al. (2017) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djx014 · Cited by 210 · see citing works
Self-citationNF-κB inhibitors in treatment and prevention of lung cancer
Rasmi, R. R., Sakthivel, K. M., & Guruvayoorappan, C. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110569 · Cited by 210 · see citing works
Targeting oncogenic Ras signaling in hematologic malignancies
Ward, A. F., Braun, B. S., & Shannon, K. (2012) · Blood · doi:10.1182/blood-2012-05-378596 · Cited by 207 · see citing works
Hypoxia and Inflammation in Cancer, Focus on HIF and NF-κB
D’Ignazio, L., Batie, M., & Rocha, S. (2017) · Biomedicines · doi:10.3390/biomedicines5020021 · Cited by 206 · see citing works
Blakely, C. M., Pazarentzos, E., Olivas, V., Asthana, S., Yan, J. J., Tan, I., Hrustanovic, G., Chan, E., Lin, L., Neel, D. S., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.03.012 · Cited by 204 · see citing works
Self-citationSantoni‐Rugiu, E., Melchior, L. C., Urbanska, E. M., Jakobsen, J. N., de Stricker, K., Grauslund, M., & Sørensen, J. B. (2019) · Cancers · doi:10.3390/cancers11070923 · Cited by 195 · see citing works
Immune Resistance in Lung Adenocarcinoma
Σπέλλα, Μ., & Stathopoulos, G. T. (2021) · Cancers · doi:10.3390/cancers13030384 · Cited by 195 · see citing works
Emerging Insights into Targeted Therapy-Tolerant Persister Cells in Cancer
Cabanos, H. F., & Hata, A. N. (2021) · Cancers · doi:10.3390/cancers13112666 · Cited by 189 · see citing works
Tumor Necrosis Factor α Blockade: An Opportunity to Tackle Breast Cancer
Mercogliano, M. F., Bruni, S., Elizalde, P. V., & Schillaci, R. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00584 · Cited by 186 · see citing works
Sabnis, A. J., & Bivona, T. G. (2019) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2018.12.009 · Cited by 183 · see citing works
Self-citationRosell, R., Dafni, U., Felip, E., Curioni-Fontecedro, A., Gautschi, O., Peters, S., Massutí, B., Palmero, R., Aix, S. P., Carcereny, E., et al. (2017) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(17)30129-7 · Cited by 182 · see citing works
Self-citationLu, X., Yu, L., Zhang, Z., Ren, X., Smaill, J. B., & Ding, K. (2018) · Medicinal Research Reviews · doi:10.1002/med.21488 · Cited by 173 · see citing works
Tuning Cytokine Receptor Signaling by Re-orienting Dimer Geometry with Surrogate Ligands
Moraga, I., Wernig, G., Wilmes, S., Gryshkova, V., Richter, C. P., Hong, W., Sinha, R., Guo, F., Fabionar, H., Wehrman, T. S., et al. (2015) · Cell · doi:10.1016/j.cell.2015.02.011 · Cited by 168 · see citing works
Therapy-induced APOBEC3A drives evolution of persistent cancer cells
Isozaki, H., Sakhtemani, R., Abbasi, A., Nikpour, N., Stanzione, M., Oh, S., Langenbucher, A., Monroe, S., Su, W., Cabanos, H. F., et al. (2023) · Nature · doi:10.1038/s41586-023-06303-1 · Cited by 162 · see citing works
Capzimin is a potent and specific inhibitor of proteasome isopeptidase Rpn11
Li, J., Yakushi, T., Parlati, F., MacKinnon, A. L., Perez, C., Ma, Y., Carter, K. P., Colayco, S., Magnuson, G., Brown, B. T., et al. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2326 · Cited by 159 · see citing works
Convergent Akt activation drives acquired EGFR inhibitor resistance in lung cancer
Jacobsen, K., Bertrán-Alamillo, J., Molina‐Vila, M. Á., Teixidó, C., Karachaliou, N., Pedersen, M. H., Castellví, J., Garzón, M., Codony, C., Codony‐Servat, J., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00450-6 · Cited by 159 · see citing works
Self-citationMolecular 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
Kim, S.-H., Ezhilarasan, R., Phillips, E. S., Gallego‐Perez, D., Sparks, A. E., Taylor, D., Ladner, K. J., Furuta, T., Sabit, H., Chhipa, R. R., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.01.005 · Cited by 155 · see citing works
Targeting the Fas/FasL signaling pathway in cancer therapy
Villa‐Morales, M., & Fernández‐Piqueras, J. (2012) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2011.628937 · Cited by 153 · see citing works
NF-κB Directly Regulates Fas Transcription to Modulate Fas-mediated Apoptosis and Tumor Suppression
Liu, F., Bardhan, K., Yang, D., Thangaraju, M., Ganapathy, V., Waller, J. L., Liles, G. B., Lee, J. R., & Liu, K. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.356279 · Cited by 149 · see citing works
Reduced cell proliferation by IKK2 depletion in a mouse lung-cancer model
Xia, Y., Yeddula, N., Leblanc, M., Ke, E., Zhang, Y., Oldfield, E., Shaw, R. J., & Verma, I. M. (2012) · Nature Cell Biology · doi:10.1038/ncb2428 · Cited by 147 · see citing works
Shi, P., Oh, Y.-T., Deng, L. H., Zhang, G., Qian, G., Zhang, S., Ren, H. J., Wu, G., Legendre, B., Anderson, E., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-1574 · Cited by 147 · see citing works
Suda, K., Mizuuchi, H., Maehara, Y., & Mitsudomi, T. (2012) · Cancer and Metastasis Reviews · doi:10.1007/s10555-012-9391-7 · Cited by 141 · see citing works
The emergence of drug resistance to targeted cancer therapies: Clinical evidence
Sarmento‐Ribeiro, A. B., Scorilas, A., Gonçalves, A. C., Efferth, T., & Trougakos, I. P. (2019) · Drug Resistance Updates · doi:10.1016/j.drup.2019.100646 · Cited by 141 · see citing works
Prescott, J. A., & Cook, S. J. (2018) · Cells · doi:10.3390/cells7090115 · Cited by 139 · see citing works
Crystal structure of the proteasomal deubiquitylation module Rpn8-Rpn11
Pathare, G. R., Nagy, I., Sledz, P., Anderson, D. J., Zhou, H.-J., Pardon, E., Steyaert, J., Förster, F. G., Bracher, A., & Baumeister, W. P. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1400546111 · Cited by 135 · see citing works
Tankyrase and the Canonical Wnt Pathway Protect Lung Cancer Cells from EGFR Inhibition
Casás‐Selves, M., Kim, J., Zhang, Z., Helfrich, B. A., Gao, D., Porter, C. C., Scarborough, H. A., Bunn, P. A., Chan, D. C. F., Tan, A. C., et al. (2012) · Cancer Research · doi:10.1158/0008-5472.can-11-2848 · Cited by 130 · see citing works
EGFR-mutated oncogene-addicted non-small cell lung cancer: Current trends and future prospects
Soria, J., Mok, T. S. K., Cappuzzo, F., & Janne, P. A. (2011) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2011.10.003 · Cited by 129 · see citing works
EGFR first- and second-generation TKIs—there is still place for them in EGFR-mutant NSCLC patients
Karachaliou, N., Fernández-Bruno, M., Bracht, J. W. P., & Rosell, R. (2018) · Translational Cancer Research · doi:10.21037/tcr.2018.10.06 · Cited by 127 · see citing works
Self-citationDella Corte, C. M., Bellevicine, C., Vicidomini, G., Vitagliano, D., Malapelle, U., Accardo, M., Fabozzi, A., Fiorelli, A., Fasano, M., Papaccio, F., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-3319 · Cited by 122 · see citing works
The Naturally Processed CD95L Elicits a c-Yes/Calcium/PI3K-Driven Cell Migration Pathway
Tauzin, S., Chaigne-Delalande, B., Selva, É., Khadra, N., Daburon, S., Contin‐Bordes, C., Blanco, P., Seyec, J. L., Ducret, T., Counillon, L., et al. (2011) · PLoS Biology · doi:10.1371/journal.pbio.1001090 · Cited by 118 · see citing works
Signaling cross-talk in the resistance to HER family receptor targeted therapy
Yamaguchi, H., Chang, S. H., Hsu, J. L., & Hung, M. (2013) · Oncogene · doi:10.1038/onc.2013.74 · Cited by 115 · see citing works
Strategies to design clinical studies to identify predictive biomarkers in cancer research
Perez‐Gracia, J. L., Sanmamed, M. F., Bosch, A., Patiño‐García, A., Schalper, K. A., Segura, V., Joaquim Bellmunt, B., Tabernero, J. M., Sweeney, C. J., Choueiri, T. K., et al. (2016) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2016.12.005 · Cited by 109 · see citing works
Third generation EGFR TKIs in EGFR-mutated NSCLC: Where are we now and where are we going
Russo, A., Franchina, T., Ricciardi, G. R. R., Smiroldo, V., Picciotto, M., Zanghì, M., Rolfo, C. D., & Adamo, V. (2017) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2017.07.003 · Cited by 109 · see citing works
Targeting EGFR in Lung Cancer: Current Standards and Developments
Díaz-Serrano, A., Gella, P., Jiménez, E., Zugazagoitia, J., & Paz-Ares Rodríguez, L. (2018) · Drugs · doi:10.1007/s40265-018-0916-4 · Cited by 108 · see citing works
Malleter, M., Tauzin, S., Bessede, A., Castellano, R., Goubard, A., Godey, F., Lévêque, J., Jézéquel, P., Campion, L., Campone, M., et al. (2013) · Cancer Research · doi:10.1158/0008-5472.can-13-1794 · Cited by 104 · see citing works
Jing, N., Du, Y., Chen, X., Bai, Q., Wang, Y., Zhang, X., Zhu, N., Zhang, J., Hou, J., Wang, Q. L., et al. (2014) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-13-0464 · Cited by 104 · see citing works
Mapping the molecular determinants of BRAF oncogene dependence in human lung cancer
Lin, L., Asthana, S., Chan, E., Bandyopadhyay, S., Martins, M. M., Olivas, V. R., Yan, J. J., Pham, L. Q., Wang, M. M., Bollag, G. E., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1320956111 · Cited by 104 · see citing works
Self-citationTherapeutic value of EGFR inhibition in CRC and NSCLC: 15 years of clinical evidence
Troiani, T., Napolitano, S., Della Corte, C. M., Martini, G., Martinelli, E., Morgillo, F., & Ciardiello, F. (2016) · ESMO Open · doi:10.1136/esmoopen-2016-000088 · Cited by 104 · see citing works
YAP-Dependent AXL Overexpression Mediates Resistance to EGFR Inhibitors in NSCLC
Ghiso, E., Migliore, C., Ciciriello, V., Morando, E., Petrelli, A., Corso, S., Luca, E. D., Gatti, G., Volante, M., & Giordano, S. (2017) · Neoplasia · doi:10.1016/j.neo.2017.10.003 · Cited by 101 · see citing works
Osimertinib in the treatment of non-small-cell lung cancer: design, development and place in therapy
Santarpía, M., Liguori, A., Karachaliou, N., González‐Cao, M., Daffinà, M. G., D’Aveni, A., Marabello, G., Altavilla, G., & Rosell, R. (2017) · Lung Cancer Targets and Therapy · doi:10.2147/lctt.s119644 · Cited by 100 · see citing works
Self-citationTNF-driven adaptive response mediates resistance to EGFR inhibition in lung cancer
Gong, K., Guo, G., Gerber, D. E., Gao, B., Peyton, M., Huang, C., Minna, J. D., Hatanpaa, K. J., Kernstine, K., Cai, L., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci96148 · Cited by 98 · see citing works
Self-citationResistance 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
Self-citationvan der Wekken, A. J., Saber, A., Hiltermann, T. J. N., Kok, K., van den -->Berg, A., & Groen, H. J. M. (2016) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2016.01.024 · Cited by 98 · see citing works
EGFR mutations in lung cancer: from tissue testing to liquid biopsy
Fenizia, F., Luca, A. D., Pasquale, R., Sacco, A., Forgione, L., Lambiase, M., Iannaccone, A., Chicchinelli, N., Franco, R., Rossi, A., et al. (2015) · Future Oncology · doi:10.2217/fon.15.23 · Cited by 94 · see citing works
Surgery for NSCLC in the era of personalized medicine
Mitsudomi, T., Suda, K., & Yatabe, Y. (2013) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2013.22 · Cited by 94 · see citing works
Cheng, H., Zhang, Z., Barrueco, R. R., Borczuk, A., Liu, H., Yu, J., Silva, J. M., Cheng, S. K., Perez-Soler, R., & Halmos, B. (2015) · Oncotarget · doi:10.18632/oncotarget.6721 · Cited by 93 · see citing works
Unveiling the link between chronic inflammation and cancer
Tripathi, S., Sharma, Y., & Kumar, D. (2025) · Metabolism Open · doi:10.1016/j.metop.2025.100347 · Cited by 91 · see citing works
Development of Dual Inhibitors Targeting Epidermal Growth Factor Receptor in Cancer Therapy
Tan, L., Zhang, J., Wang, Y., Wang, X., Wang, Y., Zhang, Z., Shuai, W., Wang, G., Chen, J., Wang, C., et al. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c01714 · Cited by 88 · 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
Nottingham, L. K., Yan, C. H., Yang, X., Si, H., Coupar, J. F., Bian, Y., Cheng, T.-F., Allen, C. T., Arun, P., Gius, D. R., et al. (2013) · Oncogene · doi:10.1038/onc.2013.49 · Cited by 87 · see citing works
Tumor necrosis factor in lung cancer: Complex roles in biology and resistance to treatment
Gong, K., Guo, G., Beckley, N. A., Zhang, Y., Yang, X., Sharma, M., & Habib, A. A. (2020) · Neoplasia · doi:10.1016/j.neo.2020.12.006 · Cited by 86 · see citing works
Targeting the FOXO1/KLF6 axis regulates EGFR signaling and treatment response
Sangodkar, J., Dhawan, N. S., Melville, H., Singh, V. J., Yuan, E., Rana, H. Q., Izadmehr, S., Farrington, C. C., Mazhar, S., Katz, S., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci62058 · Cited by 84 · see citing works
NF-κB–driven suppression of FOXO3a contributes to EGFR mutation-independent gefitinib resistance
Chiu, C., Chang, Y.-W., Kuo, K.-T., Shen, Y.-S., Liu, C., Yu, Y., Cheng, C.-C., Lee, K., Chen, F., Hsu, M.-K., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1522612113 · Cited by 82 · see citing works
Cancer gene therapy targeting cellular apoptosis machinery
Jia, L., Chen, S., & Yang, A. (2012) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2012.06.008 · Cited by 82 · see citing works
Hutti, J. E., Pfefferle, A. D., Russell, S. C., Sircar, M., Perou, C. M., & Baldwin, A. S. (2012) · Cancer Research · doi:10.1158/0008-5472.can-11-4141 · Cited by 81 · see citing works
Lin, L., & Bivona, T. G. (2012) · Chemotherapy Research and Practice · doi:10.1155/2012/817297 · Cited by 80 · see citing works
Self-citationRolfo, C. D., Giovannetti, E., Hong, D. S., Bivona, T. G., Raez, L. E., Bronte, G., Buffoni, L., Reguart, N., Santos, E. S., Germonpré, P. R., et al. (2014) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2014.05.009 · Cited by 80 · see citing works
Self-citationNonapoptotic functions of Fas/ CD 95 in the immune response
Guégan, J., & Legembre, P. (2017) · FEBS Journal · doi:10.1111/febs.14292 · Cited by 81 · see citing works
Wang, L., Dong, X., Ren, Y., Luo, J., Liu, P., Su, D., & Yang, X. (2018) · Cell Death and Disease · doi:10.1038/s41419-017-0120-6 · Cited by 79 · see citing works
CD95/Fas, Non-Apoptotic Signaling Pathways, and Kinases
Gallo, M. L., Poissonnier, A., Blanco, P., & Legembre, P. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01216 · Cited by 78 · see citing works
Milan, E., Lazzari, C., Anand, S. K., Floriani, I., Torri, V., Sorlini, C., Gregorc, V., & Bachi, A. (2012) · Journal of Proteomics · doi:10.1016/j.jprot.2012.06.022 · Cited by 78 · see citing works
Han, C., Huang, Z., Zheng, C., Wan, L., Zhang, L., Peng, S., Ding, K., Ji, H., Tian, J., & Zhang, Y. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm400463q · Cited by 76 · see citing works
Okimoto, R. A., Lin, L., Olivas, V. R., Chan, E., Markegard, E., Rymar, A., Neel, D. S., Chen, X., Hemmati, G., Bollag, G. E., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1610456113 · Cited by 76 · see citing works
Self-citation
- Authors
- Bivona, T. G., Hieronymus, H., Parker, J., Chang, K., Taron, M., Rosell, R., Moonsamy, P., Dahlman, K., Miller, V. A., Costa, C., Hannon, G., & Sawyers, C. L.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Cold Spring Harbor Laboratory (US)
- Institut Català d'Oncologia (ES)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Sawyers, Charles L.
- ORCID
- Venue
- Nature
- Published
- 2011-03
- Volume
- 471
- Issue
- 7339
- Pages
- 523-526
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3541675
- OpenAlex
- W2087955215
- Cited by
- 396
- References
- 24
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 8 · 2023: 14 · 2022: 20 · 2021: 19 · 2020: 17 · 2019: 33 · 2018: 46 · 2017: 38 · 2016: 25 · 2015: 27 · 2014: 37 · 2013: 37 · 2012: 39
- FWCI
- 37.27
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Memorial Sloan-Kettering Cancer Center
- National Cancer Institute (P01CA013106)
- 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 › NF-κB Signaling Pathways
- Keywords
- NF-κB signaling, erlotinib, EGFR tyrosine kinase inhibitors, drug resistance, IκB, c-FLIP, IκB kinase, RNAi screen, lung adenocarcinoma, apoptosis, combination therapy, treatment response biomarkers, non-smoker lung cancer
- MeSH terms
- Erlotinib Hydrochloride, Dose-Response Relationship, Drug, Humans, Lung Neoplasms, Models, Biological, Mutation, Quinazolines, Signal Transduction, Down-Regulation, NF-kappa B, Genes, erbB-1, Drug Resistance, Neoplasm, fas Receptor, I-kappa B Proteins, RNA Interference, Cell Line, Tumor, Mutant Proteins, ErbB Receptors
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