title: Management of acquired resistance to epidermal growth factor receptor kinase inhibitors in patients with advanced non-small cell lung cancer.
abstract: The widespread adoption of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors for the first-line treatment of patients with advanced EGFR-mutated non-small cell lung cancer has resulted in acquired tyrosine kinase inhibitor resistance becoming a ubiquitous clinical problem. The identification of specific mechanisms of acquired resistance has allowed a better understanding of the biology and natural history of resistant disease, but is only now starting to impact treatment decisions. Strategies for managing acquired resistance in patients with advanced non-small cell lung cancer are complex and must be adapted to the individual characteristics of each patient's cancer. Although combination chemotherapy is the presumed standard of care for most patients, prospective trial data are lacking, highlighting the importance of offering patients participation in clinical trials in this setting. Emerging data from trials of third-generation mutant-specific EGFR kinase inhibitors suggests particular promise with this class of agents.
authors.affiliation: Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts; Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.
authors.forename: Adrian G
authors.initials: AG
authors.lastname: Sacher
authors.forename: Pasi A
authors.initials: PA
authors.lastname: Jänne
authors.forename: Geoffrey R
authors.initials: GR
authors.lastname: Oxnard
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*
chemical_list: D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: acquired resistance; epidermal growth factor receptor (EGFR); non-small cell lung cancer; targeted therapy
references.citation: J Clin Oncol. 2013 Mar 1;31(7):895-902
references.pmid: 23341526
references.citation: Cancer. 2013 Jan 15;119(2):356-62
references.pmid: 22810899
references.citation: J Thorac Oncol. 2014 Mar;9(3):316-23
references.pmid: 24496004
references.citation: Lancet Oncol. 2012 May;13(5):528-38
references.pmid: 22452896
references.citation: Lancet Oncol. 2013 Sep;14(10):953-61
references.pmid: 23948351
references.citation: J Clin Invest. 2009 Oct;119(10):3000-10
references.pmid: 19759520
references.citation: Int J Cancer. 2010 Jan 1;126(1):247-55
references.pmid: 19536777
references.citation: Clin Cancer Res. 2009 Apr 15;15(8):2630-6
references.pmid: 19351754
references.citation: Clin Cancer Res. 2011 Oct 1;17(19):6298-303
references.pmid: 21856766
references.citation: J Thorac Oncol. 2013 Mar;8(3):373-84
references.pmid: 23370315
references.citation: J Thorac Oncol. 2013 Jan;8(1):96-101
references.pmid: 23207920
references.citation: J Thorac Oncol. 2012 Dec;7(12):1807-1814
references.pmid: 23154552
references.citation: J Natl Cancer Inst. 2012 Oct 17;104(20):1534-41
references.pmid: 22927506
references.citation: Clin Cancer Res. 2011 Sep 1;17(17):5530-7
references.pmid: 21775534
references.citation: Sci Transl Med. 2011 Jul 6;3(90):90ra59
references.pmid: 21734175
references.citation: Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):E2127-33
references.pmid: 22773810
references.citation: Clin Cancer Res. 2011 Mar 1;17(5):1169-80
references.pmid: 21248300
references.citation: Neuro Oncol. 2011 Dec;13(12):1364-9
references.pmid: 21865399
references.citation: Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2166-71
references.pmid: 16609030
references.citation: J Clin Oncol. 2010 Jan 10;28(2):357-60
references.pmid: 19949011
references.citation: Oncologist. 2013;18(11):1214-20
references.pmid: 24072220
references.citation: Clin Cancer Res. 2013 Apr 15;19(8):2240-7
references.pmid: 23470965
references.citation: Clin Cancer Res. 2011 Apr 15;17(8):2521-7
references.pmid: 21248303
references.citation: N Engl J Med. 2010 Jun 24;362(25):2380-8
references.pmid: 20573926
references.citation: Nat Med. 2013 Nov;19(11):1389-400
references.pmid: 24202392
references.citation: N Engl J Med. 2011 Jul 28;365(4):379-80
references.pmid: 21793762
references.citation: Nature. 2009 Dec 24;462(7276):1070-4
references.pmid: 20033049
references.citation: BMC Cancer. 2011 Jan 01;11:1
references.pmid: 21194487
references.citation: Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13306-11
references.pmid: 15329413
references.citation: J Clin Oncol. 2013 Mar 10;31(8):1070-80
references.pmid: 23401451
references.citation: J Clin Oncol. 2013 Sep 20;31(27):3327-34
references.pmid: 23816960
references.citation: N Engl J Med. 2009 Sep 3;361(10):958-67
references.pmid: 19692684
references.citation: Clin Cancer Res. 2011 Mar 15;17(6):1616-22
references.pmid: 21135146
references.citation: Clin Cancer Res. 2014 Mar 15;20(6):1698-1705
references.pmid: 24429876
references.citation: N Engl J Med. 2005 Feb 24;352(8):786-92
references.pmid: 15728811
references.citation: Cancer Res. 2007 Dec 15;67(24):11924-32
references.pmid: 18089823
references.citation: Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20932-7
references.pmid: 18093943
references.citation: J Clin Oncol. 2008 May 20;26(15):2442-9
references.pmid: 18458038
references.citation: Science. 2004 Jun 4;304(5676):1497-500
references.pmid: 15118125
references.citation: Oncogene. 2008 Aug 7;27(34):4702-11
references.pmid: 18408761
references.citation: Nat Genet. 2012 Jul 01;44(8):852-60
references.pmid: 22751098
references.citation: Ann Oncol. 2013 May;24(5):1170-9
references.pmid: 23393121
references.citation: Sci Transl Med. 2011 Mar 23;3(75):75ra26
references.pmid: 21430269
references.citation: Cancer Discov. 2011 Dec;1(7):608-25
references.pmid: 22586683
references.citation: Cancer Cell. 2010 Jan 19;17(1):77-88
references.pmid: 20129249
references.citation: Cancer. 2013 Dec 15;119(24):4325-32
references.pmid: 24105277
references.citation: Cancer Discov. 2012 Mar;2(3):227-35
references.pmid: 22448344
references.citation: Science. 2007 May 18;316(5827):1039-43
references.pmid: 17463250
references.citation: N Engl J Med. 2006 Jul 13;355(2):213-5
references.pmid: 16837691
references.citation: Cancer Discov. 2012 Oct;2(10):922-33
references.pmid: 22956644
references.citation: PLoS Med. 2005 Mar;2(3):e73
references.pmid: 15737014
references.citation: N Engl J Med. 2004 May 20;350(21):2129-39
references.pmid: 15118073
references.citation: J Thorac Oncol. 2013 Mar;8(3):346-51
references.pmid: 23407558
references.citation: J Thorac Oncol. 2013 Sep;8(9):1118-20
references.pmid: 23945382
references.citation: J Natl Cancer Inst. 2005 Mar 2;97(5):339-46
references.pmid: 15741570
references.citation: Cancer Res. 2008 Nov 15;68(22):9479-87
references.pmid: 19010923
references.citation: Lancet Oncol. 2012 Mar;13(3):239-46
references.pmid: 22285168
references.citation: Cancer Discov. 2012 Oct;2(10):934-47
references.pmid: 22961667
references.citation: Cancer Discov. 2013 Dec;3(12):1355-63
references.pmid: 24078774
references.citation: Int J Radiat Oncol Biol Phys. 2013 Apr 1;85(5):1312-8
references.pmid: 23391814
references.citation: Cancer Discov. 2013 Dec;3(12):1404-15
references.pmid: 24065731
references.citation: J Clin Invest. 2006 Oct;116(10):2695-706
references.pmid: 16906227