Tumor cells can follow distinct evolutionary paths to become resistant to epidermal growth factor receptor inhibition

Drug-tolerant but initially EGFR T790M -negative tumor cells that undergo genetic evolution to acquire resistance to EGFR inhibitors are more resistant than pre-existing EGFR T790M -positive clones to subsequent therapy. Although mechanisms of acquired resistance of epidermal growth factor receptor...

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Published in	Nature medicine Vol. 22; no. 3; pp. 262 - 269
Main Authors	Hata, Aaron N, Niederst, Matthew J, Archibald, Hannah L, Gomez-Caraballo, Maria, Siddiqui, Faria M, Mulvey, Hillary E, Maruvka, Yosef E, Ji, Fei, Bhang, Hyo-eun C, Krishnamurthy Radhakrishna, Viveksagar, Siravegna, Giulia, Hu, Haichuan, Raoof, Sana, Lockerman, Elizabeth, Kalsy, Anuj, Lee, Dana, Keating, Celina L, Ruddy, David A, Damon, Leah J, Crystal, Adam S, Costa, Carlotta, Piotrowska, Zofia, Bardelli, Alberto, Iafrate, Anthony J, Sadreyev, Ruslan I, Stegmeier, Frank, Getz, Gad, Sequist, Lecia V, Faber, Anthony C, Engelman, Jeffrey A
Format	Journal Article
Language	English
Published	New York Nature Publishing Group US 01.03.2016 Nature Publishing Group
Subjects	13/106 14/35 45/23 64/60 692/699/67/1059/2326 692/699/67/1059/602 96/2 96/95 Apoptosis - drug effects Apoptosis - genetics Biomedicine Blotting, Western Cancer Research Carcinoma, Non-Small-Cell Lung - drug therapy Carcinoma, Non-Small-Cell Lung - genetics Carcinoma, Non-Small-Cell Lung - metabolism Cell Cycle - drug effects Cell Line, Tumor Cell Survival - drug effects Development and progression Drug resistance Drug Resistance, Neoplasm - drug effects Drug Resistance, Neoplasm - genetics Drug therapy Epidermal growth factor Gene Expression Regulation, Neoplastic - drug effects Genetic aspects Humans In Vitro Techniques Infectious Diseases Inhibitor drugs Inhibitors Lung Neoplasms - drug therapy Lung Neoplasms - genetics Lung Neoplasms - metabolism Metabolic Diseases Molecular Medicine Mutation Neurons Neurosciences Protein Kinase Inhibitors - pharmacology Quinazolines - pharmacology Receptor, Epidermal Growth Factor - antagonists & inhibitors Receptor, Epidermal Growth Factor - genetics Reverse Transcriptase Polymerase Chain Reaction Risk factors RNA, Messenger - drug effects RNA, Messenger - metabolism Tumors United States
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ISSN	1078-8956 1546-170X 1546-170X
DOI	10.1038/nm.4040

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Abstract	Drug-tolerant but initially EGFR T790M -negative tumor cells that undergo genetic evolution to acquire resistance to EGFR inhibitors are more resistant than pre-existing EGFR T790M -positive clones to subsequent therapy. Although mechanisms of acquired resistance of epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancers to EGFR inhibitors have been identified, little is known about how resistant clones evolve during drug therapy. Here we observe that acquired resistance caused by the EGFR T790M gatekeeper mutation can occur either by selection of pre-existing EGFR T790M -positive clones or via genetic evolution of initially EGFR T790M -negative drug-tolerant cells. The path to resistance impacts the biology of the resistant clone, as those that evolved from drug-tolerant cells had a diminished apoptotic response to third-generation EGFR inhibitors that target EGFR T790M ; treatment with navitoclax, an inhibitor of the anti-apoptotic factors BCL-xL and BCL-2 restored sensitivity. We corroborated these findings using cultures derived directly from EGFR inhibitor–resistant patient tumors. These findings provide evidence that clinically relevant drug-resistant cancer cells can both pre-exist and evolve from drug-tolerant cells, and they point to therapeutic opportunities to prevent or overcome resistance in the clinic.
AbstractList	Although mechanisms of acquired resistance of epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancersto EGFR inhibitors have been identified, little is known about how resistant clones evolve during drug therapy. Here we observe that acquired resistance caused by the EGFRT790M gatekeeper mutation can occur either by selection of pre-existing EGFRT790M-positive clones or via genetic evolution of initially EGFRT790M-negative drug-tolerant cells. The path to resistance impacts the biology of the resistant clone, as those that evolved from drug-tolerant cells had a diminished apoptotic response to third-generation EGFR inhibitors that target EGFRT790M; treatment with navitoclax, an inhibitor of the anti-apoptotic factors BCL-xL and BCL-2 restored sensitivity. We corroborated these findings using cultures derived directly from EGFR inhibitorresistant patient tumors. T Although mechanisms of acquired resistance of epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancers to EGFR inhibitors have been identified, little is known about how resistant clones evolve during drug therapy. Here we observe that acquired resistance caused by the EGFR(T790M) gatekeeper mutation can occur either by selection of pre-existing EGFR(T790M)-positive clones or via genetic evolution of initially EGFR(T790M)-negative drug-tolerant cells. The path to resistance impacts the biology of the resistant clone, as those that evolved from drug-tolerant cells had a diminished apoptotic response to third-generation EGFR inhibitors that target EGFR(T790M); treatment with navitoclax, an inhibitor of the anti-apoptotic factors BCL-xL and BCL-2 restored sensitivity. We corroborated these findings using cultures derived directly from EGFR inhibitor-resistant patient tumors. These findings provide evidence that clinically relevant drug-resistant cancer cells can both pre-exist and evolve from drug-tolerant cells, and they point to therapeutic opportunities to prevent or overcome resistance in the clinic. Drug-tolerant but initially EGFR T790M -negative tumor cells that undergo genetic evolution to acquire resistance to EGFR inhibitors are more resistant than pre-existing EGFR T790M -positive clones to subsequent therapy. Although mechanisms of acquired resistance of epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancers to EGFR inhibitors have been identified, little is known about how resistant clones evolve during drug therapy. Here we observe that acquired resistance caused by the EGFR T790M gatekeeper mutation can occur either by selection of pre-existing EGFR T790M -positive clones or via genetic evolution of initially EGFR T790M -negative drug-tolerant cells. The path to resistance impacts the biology of the resistant clone, as those that evolved from drug-tolerant cells had a diminished apoptotic response to third-generation EGFR inhibitors that target EGFR T790M ; treatment with navitoclax, an inhibitor of the anti-apoptotic factors BCL-xL and BCL-2 restored sensitivity. We corroborated these findings using cultures derived directly from EGFR inhibitor–resistant patient tumors. These findings provide evidence that clinically relevant drug-resistant cancer cells can both pre-exist and evolve from drug-tolerant cells, and they point to therapeutic opportunities to prevent or overcome resistance in the clinic. Although mechanisms of acquired resistance of epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancers to EGFR inhibitors have been identified, little is known about how resistant clones evolve during drug therapy. Here we observe that acquired resistance caused by the EGFR(T790M) gatekeeper mutation can occur either by selection of pre-existing EGFR(T790M)-positive clones or via genetic evolution of initially EGFR(T790M)-negative drug-tolerant cells. The path to resistance impacts the biology of the resistant clone, as those that evolved from drug-tolerant cells had a diminished apoptotic response to third-generation EGFR inhibitors that target EGFR(T790M); treatment with navitoclax, an inhibitor of the anti-apoptotic factors BCL-xL and BCL-2 restored sensitivity. We corroborated these findings using cultures derived directly from EGFR inhibitor-resistant patient tumors. These findings provide evidence that clinically relevant drug-resistant cancer cells can both pre-exist and evolve from drug-tolerant cells, and they point to therapeutic opportunities to prevent or overcome resistance in the clinic.Although mechanisms of acquired resistance of epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancers to EGFR inhibitors have been identified, little is known about how resistant clones evolve during drug therapy. Here we observe that acquired resistance caused by the EGFR(T790M) gatekeeper mutation can occur either by selection of pre-existing EGFR(T790M)-positive clones or via genetic evolution of initially EGFR(T790M)-negative drug-tolerant cells. The path to resistance impacts the biology of the resistant clone, as those that evolved from drug-tolerant cells had a diminished apoptotic response to third-generation EGFR inhibitors that target EGFR(T790M); treatment with navitoclax, an inhibitor of the anti-apoptotic factors BCL-xL and BCL-2 restored sensitivity. We corroborated these findings using cultures derived directly from EGFR inhibitor-resistant patient tumors. These findings provide evidence that clinically relevant drug-resistant cancer cells can both pre-exist and evolve from drug-tolerant cells, and they point to therapeutic opportunities to prevent or overcome resistance in the clinic. Although mechanisms of acquired resistance of epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancers to EGFR inhibitors have been identified, little is known about how resistant clones evolve during drug therapy. Here we observe that acquired resistance caused by the [EGFR.sup.T790M] gatekeeper mutation can occur either by selection of pre- existing [EGFR.sup.T790M]-positive clones or via genetic evolution of initially [EGFR.sup.T790M]-negative drug-tolerant cells. The path to resistance impacts the biology of the resistant clone, as those that evolved from drug-tolerant cells had a diminished apoptotic response to third-generation EGFR inhibitors that target [EGFR.sup.T790M]; treatment with navitoclax, an inhibitor of the anti-apoptotic factors BCL-xL and BCL-2 restored sensitivity. We corroborated these findings using cultures derived directly from EGFR inhibitor- resistant patient tumors. These findings provide evidence that clinically relevant drug-resistant cancer cells can both pre-exist and evolve from drug-tolerant cells, and they point to therapeutic opportunities to prevent or overcome resistance in the clinic. Although mechanisms of acquired resistance of EGFR mutant non-small cell lung cancers to EGFR inhibitors have been identified, little is known about how resistant clones evolve during drug therapy. Here, we observe that acquired resistance caused by the T790M gatekeeper mutation can occur either by selection of pre-existing T790M clones or via genetic evolution of initially T790M-negative drug tolerant cells. The path to resistance impacts the biology of the resistant clone, as those that evolved from drug tolerant cells had a diminished apoptotic response to third generation EGFR inhibitors that target T790M EGFR; treatment with navitoclax, an inhibitor of BCL-XL and BCL-2 restored sensitivity. We corroborated these findings using cultures derived directly from EGFR inhibitor-resistant patient tumors. These findings provide evidence that clinically relevant drug resistant cancer cells can both pre-exist and evolve from drug tolerant cells, and point to therapeutic opportunities to prevent or overcome resistance in the clinic.
Audience	Academic
Author	Ji, Fei Iafrate, Anthony J Hu, Haichuan Lee, Dana Krishnamurthy Radhakrishna, Viveksagar Faber, Anthony C Damon, Leah J Sadreyev, Ruslan I Stegmeier, Frank Kalsy, Anuj Niederst, Matthew J Sequist, Lecia V Mulvey, Hillary E Bhang, Hyo-eun C Lockerman, Elizabeth Archibald, Hannah L Keating, Celina L Siravegna, Giulia Ruddy, David A Maruvka, Yosef E Siddiqui, Faria M Gomez-Caraballo, Maria Raoof, Sana Costa, Carlotta Piotrowska, Zofia Bardelli, Alberto Engelman, Jeffrey A Crystal, Adam S Hata, Aaron N Getz, Gad
AuthorAffiliation	3 Broad Institute of MIT and Harvard, Cambridge, MA, USA 1 Massachusetts General Hospital Cancer Center, Charlestown, MA, USA 5 Oncology Disease Area, Novartis Institutes for Biomedical Research, Cambridge, MA, USA 6 University of Torino, Department of Oncology, Torino, Italy 10 Department of Pathology, Harvard Medical School, Boston, MA, USA 9 Department of Pathology, Massachusetts General Hospital, Boston, MA, USA 11 Virginia Commonwealth University Philips Institute for Oral Health Research, School of Dentistry and Massey Cancer Center, Richmond, VA, USA 2 Department of Medicine, Harvard Medical School, Boston, MA, USA 7 Candiolo Cancer Institute - Fondazione Piemontese per l’Oncologia (FPO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Candiolo, Torino, Italy 4 Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA 8 Translational Clinical Oncology, Novartis Institutes for Biomedical Research, Cambridge, MA, USA
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BackLink	https://www.ncbi.nlm.nih.gov/pubmed/26828195$$D View this record in MEDLINE/PubMed
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Cites_doi	10.1146/annurev.biochem.69.1.497 10.1371/journal.pmed.0020073 10.1016/j.ccr.2009.11.022 10.1038/nature08622 10.1038/ng1180 10.1126/science.1141478 10.1126/scitranslmed.3002356 10.1126/science.1254721 10.1038/nmeth.2138 10.1158/2159-8290.CD-15-0011 10.1073/pnas.0912629107 10.1016/j.ccr.2014.05.019 10.1172/JCI35437 10.1158/0008-5472.CAN-13-3728 10.1158/2159-8290.CD-11-0106 10.1073/pnas.0506580102 10.1038/ncomms7377 10.1093/bioinformatics/bts635 10.1093/bioinformatics/btu638 10.1038/nrclinonc.2014.104 10.1056/NEJMoa0810699 10.1056/NEJMoa1411817 10.1158/2159-8290.CD-15-0399 10.1038/nm.3729 10.1093/bioinformatics/btp616 10.1158/0008-5472.CAN-14-3167 10.1126/scitranslmed.3007947 10.1371/journal.pmed.0040316 10.1038/nm.3854 10.1126/scitranslmed.3002003 10.1038/nm.3841 10.1056/NEJMoa0909530 10.1200/JCO.2011.38.3224 10.1371/journal.pmed.0040315 10.1002/emmm.201000070 10.1073/pnas.1203530109 10.1056/NEJMoa0800668 10.1038/nature12213 10.1056/NEJMoa1413654 10.1016/0165-1161(89)90001-0 10.1371/journal.pmed.0040294 10.1158/2159-8290.CD-14-0337 10.1016/j.ccr.2012.11.007 10.1158/2159-8290.CD-14-0462 10.1021/ac202028g 10.1158/1078-0432.CCR-12-1558 10.1016/j.ccell.2014.12.001 10.1126/science.1253462 10.1038/nrg3655 10.1038/nature11249 10.1097/JTO.0b013e31829f691f 10.1038/nature12477 10.1016/j.cell.2010.02.027 10.1016/j.ccell.2015.03.008
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References	Corcoran (CR31) 2013; 23 Hirata (CR37) 2015; 27 Gong (CR19) 2007; 4 Ohashi (CR24) 2012; 109 Kunkel, Bebenek (CR46) 2000; 69 Hindson (CR22) 2011; 83 Wilson (CR13) 2012; 487 CR38 de Bruin (CR32) 2014; 346 Sequist (CR28) 2015; 372 Dias-Santagata (CR42) 2010; 2 Hata, Engelman, Faber (CR16) 2015; 5 Hata (CR43) 2014; 74 Anders, Pyl, Huber (CR52) 2015; 31 Cragg (CR30) 2008; 118 Mok (CR1) 2009; 361 Eberlein (CR25) 2015; 75 Zheng (CR23) 2014; 20 Robinson, McCarthy, Smyth (CR53) 2010; 26 Thress (CR39) 2015; 21 Lynch (CR49) 2010; 107 Engelman (CR6) 2007; 316 Sequist (CR4) 2011; 3 Robasky, Lewis, Church (CR21) 2014; 15 Sharma (CR11) 2010; 141 Bhang (CR8) 2015; 21 Crystal (CR14) 2014; 346 Misale, Di Nicolantonio, Sartore-Bianchi, Siena, Bardelli (CR34) 2014; 4 Subramanian (CR54) 2005; 102 Oller, Rastogi, Morgenthaler, Thilly (CR47) 1989; 216 Lawrence (CR50) 2013; 499 Dobin (CR51) 2013; 29 Cragg, Kuroda, Puthalakath, Huang, Strasser (CR17) 2007; 4 Ye (CR10) 2013; 8 Mootha (CR55) 2003; 34 Pao (CR5) 2005; 2 Jänne (CR27) 2015; 372 Faber (CR20) 2011; 1 Maheswaran (CR35) 2008; 359 Costa (CR18) 2007; 4 Piotrowska (CR26) 2015; 5 Cross (CR29) 2014; 4 Tyson, Garbett, Frick, Quaranta (CR45) 2012; 9 Byers (CR36) 2013; 19 Chmielecki (CR44) 2011; 3 Lee (CR12) 2014; 26 Su (CR9) 2012; 30 McGranahan, Swanton (CR33) 2015; 27 Turke (CR7) 2010; 17 Zhou (CR15) 2009; 462 Maemondo (CR2) 2010; 362 Niederst (CR40) 2015; 6 Misale (CR41) 2014; 6 Alexandrov (CR48) 2013; 500 Camidge, Pao, Sequist (CR3) 2014; 11 RB Corcoran (BFnm4040_CR31) 2013; 23 AR Oller (BFnm4040_CR47) 1989; 216 MD Robinson (BFnm4040_CR53) 2010; 26 TA Kunkel (BFnm4040_CR46) 2000; 69 SV Sharma (BFnm4040_CR11) 2010; 141 MS Lawrence (BFnm4040_CR50) 2013; 499 S Misale (BFnm4040_CR41) 2014; 6 W Pao (BFnm4040_CR5) 2005; 2 LB Alexandrov (BFnm4040_CR48) 2013; 500 MS Cragg (BFnm4040_CR30) 2008; 118 J Chmielecki (BFnm4040_CR44) 2011; 3 KY Su (BFnm4040_CR9) 2012; 30 S Anders (BFnm4040_CR52) 2015; 31 S Misale (BFnm4040_CR34) 2014; 4 MJ Niederst (BFnm4040_CR40) 2015; 6 X Ye (BFnm4040_CR10) 2013; 8 HE Bhang (BFnm4040_CR8) 2015; 21 DB Costa (BFnm4040_CR18) 2007; 4 CA Eberlein (BFnm4040_CR25) 2015; 75 AC Faber (BFnm4040_CR20) 2011; 1 D Dias-Santagata (BFnm4040_CR42) 2010; 2 LV Sequist (BFnm4040_CR28) 2015; 372 LV Sequist (BFnm4040_CR4) 2011; 3 AN Hata (BFnm4040_CR43) 2014; 74 AS Crystal (BFnm4040_CR14) 2014; 346 S Maheswaran (BFnm4040_CR35) 2008; 359 DA Cross (BFnm4040_CR29) 2014; 4 Z Piotrowska (BFnm4040_CR26) 2015; 5 A Subramanian (BFnm4040_CR54) 2005; 102 M Maemondo (BFnm4040_CR2) 2010; 362 K Robasky (BFnm4040_CR21) 2014; 15 Y Gong (BFnm4040_CR19) 2007; 4 LA Byers (BFnm4040_CR36) 2013; 19 DR Tyson (BFnm4040_CR45) 2012; 9 BJ Hindson (BFnm4040_CR22) 2011; 83 BFnm4040_CR38 Z Zheng (BFnm4040_CR23) 2014; 20 K Ohashi (BFnm4040_CR24) 2012; 109 JA Engelman (BFnm4040_CR6) 2007; 316 MS Cragg (BFnm4040_CR17) 2007; 4 KS Thress (BFnm4040_CR39) 2015; 21 AN Hata (BFnm4040_CR16) 2015; 5 HJ Lee (BFnm4040_CR12) 2014; 26 DR Camidge (BFnm4040_CR3) 2014; 11 M Lynch (BFnm4040_CR49) 2010; 107 A Dobin (BFnm4040_CR51) 2013; 29 E Hirata (BFnm4040_CR37) 2015; 27 N McGranahan (BFnm4040_CR33) 2015; 27 VK Mootha (BFnm4040_CR55) 2003; 34 TS Mok (BFnm4040_CR1) 2009; 361 W Zhou (BFnm4040_CR15) 2009; 462 PA Jänne (BFnm4040_CR27) 2015; 372 TR Wilson (BFnm4040_CR13) 2012; 487 AB Turke (BFnm4040_CR7) 2010; 17 EC de Bruin (BFnm4040_CR32) 2014; 346 23945592 - Nature. 2013 Aug 22;500(7463):415-21 25934077 - Cancer Discov. 2015 Jul;5(7):713-22 22035192 - Anal Chem. 2011 Nov 15;83(22):8604-10 24675361 - Cancer Res. 2014 Jun 1;74(11):3146-56 23104886 - Bioinformatics. 2013 Jan 1;29(1):15-21 19692680 - N Engl J Med. 2009 Sep 3;361(10):947-57 24322726 - Nat Rev Genet. 2014 Jan;15(1):56-62 24893891 - Cancer Discov. 2014 Sep;4(9):1046-61 23091115 - Clin Cancer Res. 2013 Jan 1;19(1):279-90 17973573 - PLoS Med. 2007 Oct;4(10 ):1681-89; discussion 1690 15737014 - PLoS Med. 2005 Mar;2(3):e73 25849130 - Nat Med. 2015 May;21(5):440-8 2733715 - Mutat Res. 1989 Jun;216(3):149-61 25384085 - Nat Med. 2014 Dec;20(12):1479-84 25870145 - Cancer Res. 2015 Jun 15;75(12):2489-500 23770567 - Nature. 2013 Jul 11;499(7457):214-8 25260700 - Bioinformatics. 2015 Jan 15;31(2):166-9 18596266 - N Engl J Med. 2008 Jul 24;359(4):366-77 20033049 - Nature. 2009 Dec 24;462(7276):1070-4 24981256 - Nat Rev Clin Oncol. 2014 Aug;11(8):473-81 17927446 - PLoS Med. 2007 Oct 9;4(10):e294 25758528 - Nat Commun. 2015 Mar 11;6:6377 20129249 - Cancer Cell. 2010 Jan 19;17(1):77-88 25065853 - Cancer Cell. 2014 Aug 11;26(2):207-21 22215752 - J Clin Oncol. 2012 Feb 1;30(4):433-40 23945382 - J Thorac Oncol. 2013 Sep;8(9):1118-20 20432502 - EMBO Mol Med. 2010 May;2(5):146-58 18949058 - J Clin Invest. 2008 Nov;118(11):3651-9 16199517 - Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50 21734175 - Sci Transl Med. 2011 Jul 6;3(90):90ra59 17463250 - Science. 2007 May 18;316(5827):1039-43 22763448 - Nature. 2012 Jul 26;487(7408):505-9 20080596 - Proc Natl Acad Sci U S A. 2010 Jan 19;107(3):961-8 22773810 - Proc Natl Acad Sci U S A. 2012 Jul 31;109 (31):E2127-33 22145099 - Cancer Discov. 2011 Sep;1(4):352-65 25939061 - Nat Med. 2015 Jun;21(6):560-2 25873177 - Cancer Cell. 2015 Apr 13;27(4):574-88 25301630 - Science. 2014 Oct 10;346(6206):251-6 22886092 - Nat Methods. 2012 Sep;9(9):923-8 20573926 - N Engl J Med. 2010 Jun 24;362(25):2380-8 20371346 - Cell. 2010 Apr 2;141(1):69-80 26911183 - Nat Rev Cancer. 2016 Mar;16(3):128 17973572 - PLoS Med. 2007 Oct;4(10 ):1669-79; discussion 1680 24553387 - Sci Transl Med. 2014 Feb 19;6(224):224ra26 19910308 - Bioinformatics. 2010 Jan 1;26(1):139-40 25394791 - Science. 2014 Dec 19;346(6216):1480-6 25923550 - N Engl J Med. 2015 Apr 30;372(18):1700-9 21430269 - Sci Transl Med. 2011 Mar 23;3(75):75ra26 25895919 - Cancer Discov. 2015 May;5(5):475-87 23245996 - Cancer Cell. 2013 Jan 14;23(1):121-8 12808457 - Nat Genet. 2003 Jul;34(3):267-73 10966467 - Annu Rev Biochem. 2000;69:497-529 25584892 - Cancer Cell. 2015 Jan 12;27(1):15-26 25923549 - N Engl J Med. 2015 Apr 30;372(18):1689-99 25293556 - Cancer Discov. 2014 Nov;4(11):1269-80
References_xml	– volume: 69 start-page: 497 year: 2000 end-page: 529 ident: CR46 article-title: DNA replication fidelity publication-title: Annu. Rev. Biochem. doi: 10.1146/annurev.biochem.69.1.497 – volume: 2 start-page: e73 year: 2005 ident: CR5 article-title: Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain publication-title: PLoS Med. doi: 10.1371/journal.pmed.0020073 – volume: 17 start-page: 77 year: 2010 end-page: 88 ident: CR7 article-title: Preexistence and clonal selection of MET amplification in EGFR-mutant NSCLC publication-title: Cancer Cell doi: 10.1016/j.ccr.2009.11.022 – volume: 462 start-page: 1070 year: 2009 end-page: 1074 ident: CR15 article-title: Novel mutant-selective EGFR kinase inhibitors against EGFR publication-title: Nature doi: 10.1038/nature08622 – volume: 34 start-page: 267 year: 2003 end-page: 273 ident: CR55 article-title: PGC-1α–responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes publication-title: Nat. Genet. doi: 10.1038/ng1180 – volume: 316 start-page: 1039 year: 2007 end-page: 1043 ident: CR6 article-title: MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling publication-title: Science doi: 10.1126/science.1141478 – volume: 3 start-page: 90ra59 year: 2011 ident: CR44 article-title: Optimization of dosing for EGFR-mutant non-small-cell lung cancer with evolutionary cancer modeling publication-title: Sci. Transl. Med. doi: 10.1126/scitranslmed.3002356 – volume: 346 start-page: 1480 year: 2014 end-page: 1486 ident: CR14 article-title: Patient-derived models of acquired resistance can identify effective drug combinations for cancer publication-title: Science doi: 10.1126/science.1254721 – volume: 9 start-page: 923 year: 2012 end-page: 928 ident: CR45 article-title: Fractional proliferation: a method to deconvolve cell population dynamics from single-cell data publication-title: Nat. Methods doi: 10.1038/nmeth.2138 – volume: 5 start-page: 475 year: 2015 end-page: 487 ident: CR16 article-title: The BCL2 family: key mediators of the apoptotic response to targeted anticancer therapeutics publication-title: Cancer Discov. doi: 10.1158/2159-8290.CD-15-0011 – volume: 107 start-page: 961 year: 2010 end-page: 968 ident: CR49 article-title: Rate, molecular spectrum and consequences of human mutation publication-title: Proc. Natl. Acad. Sci. USA doi: 10.1073/pnas.0912629107 – volume: 26 start-page: 207 year: 2014 end-page: 221 ident: CR12 article-title: Drug resistance via feedback activation of Stat3 in oncogene-addicted cancer cells publication-title: Cancer Cell doi: 10.1016/j.ccr.2014.05.019 – volume: 118 start-page: 3651 year: 2008 end-page: 3659 ident: CR30 article-title: Treatment of BRAF–mutant human tumor cells with a MEK inhibitor requires Bim and is enhanced by a BH3 mimetic publication-title: J. Clin. Invest. doi: 10.1172/JCI35437 – volume: 74 start-page: 3146 year: 2014 end-page: 3156 ident: CR43 article-title: Failure to induce apoptosis via BCL-2 family proteins underlies lack of efficacy of combined MEK and PI3K inhibitors for KRAS-mutant lung cancers publication-title: Cancer Res. doi: 10.1158/0008-5472.CAN-13-3728 – volume: 1 start-page: 352 year: 2011 end-page: 365 ident: CR20 article-title: BIM expression in treatment-naive cancers predicts responsiveness to kinase inhibitors publication-title: Cancer Discov. doi: 10.1158/2159-8290.CD-11-0106 – volume: 102 start-page: 15545 year: 2005 end-page: 15550 ident: CR54 article-title: Gene-set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles publication-title: Proc. Natl. Acad. Sci. USA doi: 10.1073/pnas.0506580102 – volume: 6 start-page: 6377 year: 2015 ident: CR40 article-title: RB loss in resistant EGFR-mutant lung adenocarcinomas that transform to small-cell lung cancer publication-title: Nat. Commun. doi: 10.1038/ncomms7377 – volume: 29 start-page: 15 year: 2013 end-page: 21 ident: CR51 article-title: STAR: ultrafast universal RNA-seq aligner publication-title: Bioinformatics doi: 10.1093/bioinformatics/bts635 – volume: 31 start-page: 166 year: 2015 end-page: 169 ident: CR52 article-title: HTSeq—a Python framework to work with high-throughput sequencing data publication-title: Bioinformatics doi: 10.1093/bioinformatics/btu638 – volume: 11 start-page: 473 year: 2014 end-page: 481 ident: CR3 article-title: Acquired resistance to TKIs in solid tumors: learning from lung cancer publication-title: Nat. Rev. Clin. Oncol. doi: 10.1038/nrclinonc.2014.104 – volume: 361 start-page: 947 year: 2009 end-page: 957 ident: CR1 article-title: Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma publication-title: N. Engl. J. Med. doi: 10.1056/NEJMoa0810699 – volume: 372 start-page: 1689 year: 2015 end-page: 1699 ident: CR27 article-title: AZD9291 in EGFR inhibitor–resistant non-small-cell lung cancer publication-title: N. Engl. J. Med. doi: 10.1056/NEJMoa1411817 – volume: 5 start-page: 713 year: 2015 end-page: 722 ident: CR26 article-title: Heterogeneity underlies the emergence of wild-type clones following treatment of T790M-positive cancers with a third-generation EGFR inhibitor publication-title: Cancer Discov. doi: 10.1158/2159-8290.CD-15-0399 – volume: 20 start-page: 1479 year: 2014 end-page: 1484 ident: CR23 article-title: Anchored multiplex PCR for targeted next-generation sequencing publication-title: Nat. Med. doi: 10.1038/nm.3729 – volume: 26 start-page: 139 year: 2010 end-page: 140 ident: CR53 article-title: edgeR: a Bioconductor package for differential expression analysis of digital gene-expression data publication-title: Bioinformatics doi: 10.1093/bioinformatics/btp616 – volume: 75 start-page: 2489 year: 2015 end-page: 2500 ident: CR25 article-title: Acquired resistance to the mutant-selective EGFR inhibitor AZD9291 is associated with increased dependence on RAS signaling in preclinical models publication-title: Cancer Res. doi: 10.1158/0008-5472.CAN-14-3167 – volume: 6 start-page: 224ra26 year: 2014 ident: CR41 article-title: Blockade of EGFR and MEK intercepts heterogeneous mechanisms of acquired resistance to anti-EGFR therapies in colorectal cancer publication-title: Sci. Transl. Med. doi: 10.1126/scitranslmed.3007947 – volume: 4 start-page: 1681 year: 2007 end-page: 1689 ident: CR17 article-title: Gefitinib-induced killing of NSCLC cell lines expressing mutant EGFR requires BIM and can be enhanced by BH3 mimetics publication-title: PLoS Med. doi: 10.1371/journal.pmed.0040316 – volume: 21 start-page: 560 year: 2015 end-page: 562 ident: CR39 article-title: Acquired mutation mediates resistance to AZD9291 in non-small-cell lung cancer harboring publication-title: Nat. Med. doi: 10.1038/nm.3854 – volume: 3 start-page: 75ra26 year: 2011 ident: CR4 article-title: Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors publication-title: Sci. Transl. Med. doi: 10.1126/scitranslmed.3002003 – volume: 21 start-page: 440 year: 2015 end-page: 448 ident: CR8 article-title: Studying clonal dynamics in response to cancer therapy using high-complexity barcoding publication-title: Nat. Med. doi: 10.1038/nm.3841 – volume: 362 start-page: 2380 year: 2010 end-page: 2388 ident: CR2 article-title: Gefitinib or chemotherapy for non-small-cell lung cancer with mutated publication-title: N. Engl. J. Med. doi: 10.1056/NEJMoa0909530 – volume: 30 start-page: 433 year: 2012 end-page: 440 ident: CR9 article-title: Pretreatment epidermal growth factor receptor ( ) T790M mutation predicts shorter EGFR tyrosine kinase inhibitor response duration in patients with non-small-cell lung cancer publication-title: J. Clin. Oncol. doi: 10.1200/JCO.2011.38.3224 – volume: 4 start-page: 1669 year: 2007 end-page: 1679 ident: CR18 article-title: BIM mediates EGFR tyrosine kinase inhibitor–induced apoptosis in lung cancers with oncogenic mutations publication-title: PLoS Med. doi: 10.1371/journal.pmed.0040315 – volume: 2 start-page: 146 year: 2010 end-page: 158 ident: CR42 article-title: Rapid targeted mutational analysis of human tumors: a clinical platform to guide personalized cancer medicine publication-title: EMBO Mol. Med. doi: 10.1002/emmm.201000070 – volume: 109 start-page: E2127 year: 2012 end-page: E2133 ident: CR24 article-title: Lung cancers with acquired resistance to EGFR inhibitors occasionally harbor gene mutations but lack mutations in , or publication-title: Proc. Natl. Acad. Sci. USA doi: 10.1073/pnas.1203530109 – volume: 359 start-page: 366 year: 2008 end-page: 377 ident: CR35 article-title: Detection of mutations in in circulating lung cancer cells publication-title: N. Engl. J. Med. doi: 10.1056/NEJMoa0800668 – volume: 499 start-page: 214 year: 2013 end-page: 218 ident: CR50 article-title: Mutational heterogeneity in cancer and the search for new cancer-associated genes publication-title: Nature doi: 10.1038/nature12213 – volume: 372 start-page: 1700 year: 2015 end-page: 1709 ident: CR28 article-title: Rociletinib in EGFR-mutated non-small-cell lung cancer publication-title: N. Engl. J. Med. doi: 10.1056/NEJMoa1413654 – volume: 216 start-page: 149 year: 1989 end-page: 161 ident: CR47 article-title: A statistical model to estimate variance in long-term, low-dose mutation assays: testing of the model in a human lymphoblastoid mutation assay publication-title: Mutat. Res. doi: 10.1016/0165-1161(89)90001-0 – volume: 4 start-page: e294 year: 2007 ident: CR19 article-title: Induction of BIM is essential for apoptosis triggered by EGFR kinase inhibitors in mutant EGFR-dependent lung adenocarcinomas publication-title: PLoS Med. doi: 10.1371/journal.pmed.0040294 – volume: 4 start-page: 1046 year: 2014 end-page: 1061 ident: CR29 article-title: AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer publication-title: Cancer Discov. doi: 10.1158/2159-8290.CD-14-0337 – volume: 23 start-page: 121 year: 2013 end-page: 128 ident: CR31 article-title: Synthetic lethal interaction of combined BCL-XL and MEK inhibition promotes tumor regressions in KRAS-mutant cancer models publication-title: Cancer Cell doi: 10.1016/j.ccr.2012.11.007 – volume: 4 start-page: 1269 year: 2014 end-page: 1280 ident: CR34 article-title: Resistance to anti-EGFR therapy in colorectal cancer: from heterogeneity to convergent evolution publication-title: Cancer Discov. doi: 10.1158/2159-8290.CD-14-0462 – volume: 83 start-page: 8604 year: 2011 end-page: 8610 ident: CR22 article-title: High-throughput droplet digital PCR system for absolute quantitation of DNA copy number publication-title: Anal. Chem. doi: 10.1021/ac202028g – volume: 19 start-page: 279 year: 2013 end-page: 290 ident: CR36 article-title: An epithelial-mesenchymal transition gene signature predicts resistance to EGFR and PI3K inhibitors and identifies Axl as a therapeutic target for overcoming EGFR-inhibitor resistance publication-title: Clin. Cancer Res. doi: 10.1158/1078-0432.CCR-12-1558 – ident: CR38 – volume: 27 start-page: 15 year: 2015 end-page: 26 ident: CR33 article-title: Biological and therapeutic impact of intratumor heterogeneity in cancer evolution publication-title: Cancer Cell doi: 10.1016/j.ccell.2014.12.001 – volume: 346 start-page: 251 year: 2014 end-page: 256 ident: CR32 article-title: Spatial and temporal diversity in genomic instability processes defines lung cancer evolution publication-title: Science doi: 10.1126/science.1253462 – volume: 15 start-page: 56 year: 2014 end-page: 62 ident: CR21 article-title: The role of replicates for error mitigation in next-generation sequencing publication-title: Nat. Rev. Genet. doi: 10.1038/nrg3655 – volume: 487 start-page: 505 year: 2012 end-page: 509 ident: CR13 article-title: Widespread potential for growth factor–driven resistance to anticancer kinase inhibitors publication-title: Nature doi: 10.1038/nature11249 – volume: 8 start-page: 1118 year: 2013 end-page: 1120 ident: CR10 article-title: High T790M detection rate in TKI-naive NSCLC with -sensitive mutation: truth or artifact? publication-title: J. Thorac. Oncol. doi: 10.1097/JTO.0b013e31829f691f – volume: 500 start-page: 415 year: 2013 end-page: 421 ident: CR48 article-title: Signatures of mutational processes in human cancer publication-title: Nature doi: 10.1038/nature12477 – volume: 141 start-page: 69 year: 2010 end-page: 80 ident: CR11 article-title: A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations publication-title: Cell doi: 10.1016/j.cell.2010.02.027 – volume: 27 start-page: 574 year: 2015 end-page: 588 ident: CR37 article-title: Intravital imaging reveals how BRAF inhibition generates drug-tolerant microenvironments with high integrin-β1 and FAK signaling publication-title: Cancer Cell doi: 10.1016/j.ccell.2015.03.008 – volume: 316 start-page: 1039 year: 2007 ident: BFnm4040_CR6 publication-title: Science doi: 10.1126/science.1141478 – volume: 216 start-page: 149 year: 1989 ident: BFnm4040_CR47 publication-title: Mutat. Res. doi: 10.1016/0165-1161(89)90001-0 – volume: 29 start-page: 15 year: 2013 ident: BFnm4040_CR51 publication-title: Bioinformatics doi: 10.1093/bioinformatics/bts635 – volume: 75 start-page: 2489 year: 2015 ident: BFnm4040_CR25 publication-title: Cancer Res. doi: 10.1158/0008-5472.CAN-14-3167 – volume: 31 start-page: 166 year: 2015 ident: BFnm4040_CR52 publication-title: Bioinformatics doi: 10.1093/bioinformatics/btu638 – volume: 2 start-page: e73 year: 2005 ident: BFnm4040_CR5 publication-title: PLoS Med. doi: 10.1371/journal.pmed.0020073 – volume: 30 start-page: 433 year: 2012 ident: BFnm4040_CR9 publication-title: J. Clin. Oncol. doi: 10.1200/JCO.2011.38.3224 – volume: 26 start-page: 207 year: 2014 ident: BFnm4040_CR12 publication-title: Cancer Cell doi: 10.1016/j.ccr.2014.05.019 – volume: 8 start-page: 1118 year: 2013 ident: BFnm4040_CR10 publication-title: J. Thorac. Oncol. doi: 10.1097/JTO.0b013e31829f691f – volume: 27 start-page: 574 year: 2015 ident: BFnm4040_CR37 publication-title: Cancer Cell doi: 10.1016/j.ccell.2015.03.008 – volume: 118 start-page: 3651 year: 2008 ident: BFnm4040_CR30 publication-title: J. Clin. Invest. doi: 10.1172/JCI35437 – volume: 6 start-page: 224ra26 year: 2014 ident: BFnm4040_CR41 publication-title: Sci. Transl. Med. doi: 10.1126/scitranslmed.3007947 – volume: 17 start-page: 77 year: 2010 ident: BFnm4040_CR7 publication-title: Cancer Cell doi: 10.1016/j.ccr.2009.11.022 – volume: 21 start-page: 440 year: 2015 ident: BFnm4040_CR8 publication-title: Nat. Med. doi: 10.1038/nm.3841 – volume: 109 start-page: E2127 year: 2012 ident: BFnm4040_CR24 publication-title: Proc. Natl. Acad. Sci. USA doi: 10.1073/pnas.1203530109 – volume: 27 start-page: 15 year: 2015 ident: BFnm4040_CR33 publication-title: Cancer Cell doi: 10.1016/j.ccell.2014.12.001 – volume: 372 start-page: 1689 year: 2015 ident: BFnm4040_CR27 publication-title: N. Engl. J. Med. doi: 10.1056/NEJMoa1411817 – volume: 9 start-page: 923 year: 2012 ident: BFnm4040_CR45 publication-title: Nat. Methods doi: 10.1038/nmeth.2138 – volume: 346 start-page: 251 year: 2014 ident: BFnm4040_CR32 publication-title: Science doi: 10.1126/science.1253462 – volume: 74 start-page: 3146 year: 2014 ident: BFnm4040_CR43 publication-title: Cancer Res. doi: 10.1158/0008-5472.CAN-13-3728 – volume: 487 start-page: 505 year: 2012 ident: BFnm4040_CR13 publication-title: Nature doi: 10.1038/nature11249 – ident: BFnm4040_CR38 – volume: 21 start-page: 560 year: 2015 ident: BFnm4040_CR39 publication-title: Nat. Med. doi: 10.1038/nm.3854 – volume: 361 start-page: 947 year: 2009 ident: BFnm4040_CR1 publication-title: N. Engl. J. Med. doi: 10.1056/NEJMoa0810699 – volume: 15 start-page: 56 year: 2014 ident: BFnm4040_CR21 publication-title: Nat. Rev. Genet. doi: 10.1038/nrg3655 – volume: 4 start-page: e294 year: 2007 ident: BFnm4040_CR19 publication-title: PLoS Med. doi: 10.1371/journal.pmed.0040294 – volume: 499 start-page: 214 year: 2013 ident: BFnm4040_CR50 publication-title: Nature doi: 10.1038/nature12213 – volume: 4 start-page: 1669 year: 2007 ident: BFnm4040_CR18 publication-title: PLoS Med. doi: 10.1371/journal.pmed.0040315 – volume: 5 start-page: 475 year: 2015 ident: BFnm4040_CR16 publication-title: Cancer Discov. doi: 10.1158/2159-8290.CD-15-0011 – volume: 346 start-page: 1480 year: 2014 ident: BFnm4040_CR14 publication-title: Science doi: 10.1126/science.1254721 – volume: 1 start-page: 352 year: 2011 ident: BFnm4040_CR20 publication-title: Cancer Discov. doi: 10.1158/2159-8290.CD-11-0106 – volume: 2 start-page: 146 year: 2010 ident: BFnm4040_CR42 publication-title: EMBO Mol. Med. doi: 10.1002/emmm.201000070 – volume: 6 start-page: 6377 year: 2015 ident: BFnm4040_CR40 publication-title: Nat. Commun. doi: 10.1038/ncomms7377 – volume: 500 start-page: 415 year: 2013 ident: BFnm4040_CR48 publication-title: Nature doi: 10.1038/nature12477 – volume: 362 start-page: 2380 year: 2010 ident: BFnm4040_CR2 publication-title: N. Engl. J. Med. doi: 10.1056/NEJMoa0909530 – volume: 23 start-page: 121 year: 2013 ident: BFnm4040_CR31 publication-title: Cancer Cell doi: 10.1016/j.ccr.2012.11.007 – volume: 34 start-page: 267 year: 2003 ident: BFnm4040_CR55 publication-title: Nat. Genet. doi: 10.1038/ng1180 – volume: 4 start-page: 1269 year: 2014 ident: BFnm4040_CR34 publication-title: Cancer Discov. doi: 10.1158/2159-8290.CD-14-0462 – volume: 462 start-page: 1070 year: 2009 ident: BFnm4040_CR15 publication-title: Nature doi: 10.1038/nature08622 – volume: 107 start-page: 961 year: 2010 ident: BFnm4040_CR49 publication-title: Proc. Natl. Acad. Sci. USA doi: 10.1073/pnas.0912629107 – volume: 69 start-page: 497 year: 2000 ident: BFnm4040_CR46 publication-title: Annu. Rev. Biochem. doi: 10.1146/annurev.biochem.69.1.497 – volume: 5 start-page: 713 year: 2015 ident: BFnm4040_CR26 publication-title: Cancer Discov. doi: 10.1158/2159-8290.CD-15-0399 – volume: 11 start-page: 473 year: 2014 ident: BFnm4040_CR3 publication-title: Nat. Rev. Clin. Oncol. doi: 10.1038/nrclinonc.2014.104 – volume: 141 start-page: 69 year: 2010 ident: BFnm4040_CR11 publication-title: Cell doi: 10.1016/j.cell.2010.02.027 – volume: 102 start-page: 15545 year: 2005 ident: BFnm4040_CR54 publication-title: Proc. Natl. Acad. Sci. USA doi: 10.1073/pnas.0506580102 – volume: 26 start-page: 139 year: 2010 ident: BFnm4040_CR53 publication-title: Bioinformatics doi: 10.1093/bioinformatics/btp616 – volume: 20 start-page: 1479 year: 2014 ident: BFnm4040_CR23 publication-title: Nat. Med. doi: 10.1038/nm.3729 – volume: 4 start-page: 1046 year: 2014 ident: BFnm4040_CR29 publication-title: Cancer Discov. doi: 10.1158/2159-8290.CD-14-0337 – volume: 4 start-page: 1681 year: 2007 ident: BFnm4040_CR17 publication-title: PLoS Med. doi: 10.1371/journal.pmed.0040316 – volume: 19 start-page: 279 year: 2013 ident: BFnm4040_CR36 publication-title: Clin. Cancer Res. doi: 10.1158/1078-0432.CCR-12-1558 – volume: 372 start-page: 1700 year: 2015 ident: BFnm4040_CR28 publication-title: N. Engl. J. Med. doi: 10.1056/NEJMoa1413654 – volume: 3 start-page: 90ra59 year: 2011 ident: BFnm4040_CR44 publication-title: Sci. Transl. Med. doi: 10.1126/scitranslmed.3002356 – volume: 3 start-page: 75ra26 year: 2011 ident: BFnm4040_CR4 publication-title: Sci. Transl. Med. doi: 10.1126/scitranslmed.3002003 – volume: 83 start-page: 8604 year: 2011 ident: BFnm4040_CR22 publication-title: Anal. Chem. doi: 10.1021/ac202028g – volume: 359 start-page: 366 year: 2008 ident: BFnm4040_CR35 publication-title: N. Engl. J. Med. doi: 10.1056/NEJMoa0800668 – reference: 24675361 - Cancer Res. 2014 Jun 1;74(11):3146-56 – reference: 23945382 - J Thorac Oncol. 2013 Sep;8(9):1118-20 – reference: 25873177 - Cancer Cell. 2015 Apr 13;27(4):574-88 – reference: 25870145 - Cancer Res. 2015 Jun 15;75(12):2489-500 – reference: 15737014 - PLoS Med. 2005 Mar;2(3):e73 – reference: 22145099 - Cancer Discov. 2011 Sep;1(4):352-65 – reference: 25065853 - Cancer Cell. 2014 Aug 11;26(2):207-21 – reference: 25260700 - Bioinformatics. 2015 Jan 15;31(2):166-9 – reference: 25934077 - Cancer Discov. 2015 Jul;5(7):713-22 – reference: 19910308 - Bioinformatics. 2010 Jan 1;26(1):139-40 – reference: 22035192 - Anal Chem. 2011 Nov 15;83(22):8604-10 – reference: 10966467 - Annu Rev Biochem. 2000;69:497-529 – reference: 24553387 - Sci Transl Med. 2014 Feb 19;6(224):224ra26 – reference: 23104886 - Bioinformatics. 2013 Jan 1;29(1):15-21 – reference: 25301630 - Science. 2014 Oct 10;346(6206):251-6 – reference: 25923550 - N Engl J Med. 2015 Apr 30;372(18):1700-9 – reference: 25394791 - Science. 2014 Dec 19;346(6216):1480-6 – reference: 17463250 - Science. 2007 May 18;316(5827):1039-43 – reference: 22773810 - Proc Natl Acad Sci U S A. 2012 Jul 31;109 (31):E2127-33 – reference: 24893891 - Cancer Discov. 2014 Sep;4(9):1046-61 – reference: 25758528 - Nat Commun. 2015 Mar 11;6:6377 – reference: 23945592 - Nature. 2013 Aug 22;500(7463):415-21 – reference: 25293556 - Cancer Discov. 2014 Nov;4(11):1269-80 – reference: 22763448 - Nature. 2012 Jul 26;487(7408):505-9 – reference: 24322726 - Nat Rev Genet. 2014 Jan;15(1):56-62 – reference: 23245996 - Cancer Cell. 2013 Jan 14;23(1):121-8 – reference: 25384085 - Nat Med. 2014 Dec;20(12):1479-84 – reference: 17973572 - PLoS Med. 2007 Oct;4(10 ):1669-79; discussion 1680 – reference: 24981256 - Nat Rev Clin Oncol. 2014 Aug;11(8):473-81 – reference: 26911183 - Nat Rev Cancer. 2016 Mar;16(3):128 – reference: 21430269 - Sci Transl Med. 2011 Mar 23;3(75):75ra26 – reference: 21734175 - Sci Transl Med. 2011 Jul 6;3(90):90ra59 – reference: 12808457 - Nat Genet. 2003 Jul;34(3):267-73 – reference: 25939061 - Nat Med. 2015 Jun;21(6):560-2 – reference: 20033049 - Nature. 2009 Dec 24;462(7276):1070-4 – reference: 22886092 - Nat Methods. 2012 Sep;9(9):923-8 – reference: 20080596 - Proc Natl Acad Sci U S A. 2010 Jan 19;107(3):961-8 – reference: 18949058 - J Clin Invest. 2008 Nov;118(11):3651-9 – reference: 2733715 - Mutat Res. 1989 Jun;216(3):149-61 – reference: 25895919 - Cancer Discov. 2015 May;5(5):475-87 – reference: 23770567 - Nature. 2013 Jul 11;499(7457):214-8 – reference: 22215752 - J Clin Oncol. 2012 Feb 1;30(4):433-40 – reference: 17973573 - PLoS Med. 2007 Oct;4(10 ):1681-89; discussion 1690 – reference: 25584892 - Cancer Cell. 2015 Jan 12;27(1):15-26 – reference: 18596266 - N Engl J Med. 2008 Jul 24;359(4):366-77 – reference: 25849130 - Nat Med. 2015 May;21(5):440-8 – reference: 19692680 - N Engl J Med. 2009 Sep 3;361(10):947-57 – reference: 20129249 - Cancer Cell. 2010 Jan 19;17(1):77-88 – reference: 25923549 - N Engl J Med. 2015 Apr 30;372(18):1689-99 – reference: 20432502 - EMBO Mol Med. 2010 May;2(5):146-58 – reference: 17927446 - PLoS Med. 2007 Oct 9;4(10):e294 – reference: 16199517 - Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50 – reference: 20371346 - Cell. 2010 Apr 2;141(1):69-80 – reference: 20573926 - N Engl J Med. 2010 Jun 24;362(25):2380-8 – reference: 23091115 - Clin Cancer Res. 2013 Jan 1;19(1):279-90
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Snippet	Drug-tolerant but initially EGFR T790M -negative tumor cells that undergo genetic evolution to acquire resistance to EGFR inhibitors are more resistant than... Although mechanisms of acquired resistance of epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancers to EGFR inhibitors have been... Although mechanisms of acquired resistance of epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancersto EGFR inhibitors have been... Although mechanisms of acquired resistance of EGFR mutant non-small cell lung cancers to EGFR inhibitors have been identified, little is known about how...
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SubjectTerms	13/106 14/35 45/23 64/60 692/699/67/1059/2326 692/699/67/1059/602 96/2 96/95 Apoptosis - drug effects Apoptosis - genetics Biomedicine Blotting, Western Cancer Research Carcinoma, Non-Small-Cell Lung - drug therapy Carcinoma, Non-Small-Cell Lung - genetics Carcinoma, Non-Small-Cell Lung - metabolism Cell Cycle - drug effects Cell Line, Tumor Cell Survival - drug effects Development and progression Drug resistance Drug Resistance, Neoplasm - drug effects Drug Resistance, Neoplasm - genetics Drug therapy Epidermal growth factor Gene Expression Regulation, Neoplastic - drug effects Genetic aspects Humans In Vitro Techniques Infectious Diseases Inhibitor drugs Inhibitors Lung Neoplasms - drug therapy Lung Neoplasms - genetics Lung Neoplasms - metabolism Metabolic Diseases Molecular Medicine Mutation Neurons Neurosciences Protein Kinase Inhibitors - pharmacology Quinazolines - pharmacology Receptor, Epidermal Growth Factor - antagonists & inhibitors Receptor, Epidermal Growth Factor - genetics Reverse Transcriptase Polymerase Chain Reaction Risk factors RNA, Messenger - drug effects RNA, Messenger - metabolism Tumors
Title	Tumor cells can follow distinct evolutionary paths to become resistant to epidermal growth factor receptor inhibition
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