title: New targetable oncogenes in non-small-cell lung cancer.
abstract: The identification of oncogenic driver mutations underlying sensitivity to epidermal growth factor receptor and anaplastic lymphoma kinase tyrosine kinase inhibitors has led to a surge of interest in identifying additional targetable oncogenes in non-small-cell lung cancer. A number of new potentially oncogenic gene alterations have been characterized in recent years, including BRAF mutations, HER2 insertions, PIK3CA mutations, FGFR1 amplifications, DDR2 mutations, ROS1 rearrangements, and RET rearrangements. In this review, we will discuss the techniques used to discover each of these candidate oncogenes, the prevalence of each in non-small-cell lung cancer, the preclinical data supporting their role in lung cancer, and data on small molecular inhibitors in development.
authors: Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA 02215, USA.
authors: Geoffrey R
authors: GR
authors: Oxnard
authors: Adam
authors: A
authors: Binder
authors: Pasi A
authors: PA
authors: Jänne
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D058534:Class I Phosphatidylinositol 3-Kinases; D004252:DNA Mutational Analysis; D000070819:Discoidin Domain Receptor 1; D015972:Gene Expression Regulation, Neoplastic; D005821:Genetic Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D009857:Oncogenes; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics
chemical_list: D058534:Class I Phosphatidylinositol 3-Kinases; D000070819:Discoidin Domain Receptor 1; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D048493:Proto-Oncogene Proteins B-raf; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; C484760:PIK3CA protein, human; C092030:DDR1 protein, human; C496348:FGFR1 protein, human; C062333:ROS1 protein, human; C482119:BRAF protein, human
references: Nat Med. 2012 Feb 12;18(3):378-81
references: 22327623
references: N Engl J Med. 2006 Dec 14;355(24):2542-50
references: 17167137
references: Cancer Res. 2008 Sep 1;68(17):6913-21
references: 18757405
references: N Engl J Med. 2011 Jun 16;364(24):2305-15
references: 21663470
references: J Clin Oncol. 2009 Mar 10;27(8):1227-34
references: 19188680
references: Cell. 2004 Mar 19;116(6):855-67
references: 15035987
references: Clin Cancer Res. 2012 Feb 15;18(4):1167-76
references: 22228640
references: Lancet. 2010 Aug 28;376(9742):687-97
references: 20728210
references: Ann Oncol. 2011 Jun;22(6):1413-1419
references: 21131369
references: N Engl J Med. 2009 Sep 3;361(10):947-57
references: 19692680
references: J Clin Oncol. 2012 Mar 10;30(8):765-6
references: 22271482
references: N Engl J Med. 2005 Jul 14;353(2):123-32
references: 16014882
references: Cancer Res. 2008 May 1;68(9):3389-95
references: 18451166
references: J Clin Oncol. 2010 Dec 10;28(35):5219-28
references: 20975063
references: Genome Res. 2012 Mar;22(3):436-45
references: 22194472
references: Ann Oncol. 2011 Dec;22(12):2616-2624
references: 22071650
references: N Engl J Med. 2010 Aug 26;363(9):809-19
references: 20818844
references: J Clin Oncol. 2011 Sep 10;29(26):3574-9
references: 21825258
references: N Engl J Med. 2012 Jul 12;367(2):107-14
references: 22663011
references: Cell. 2007 Dec 14;131(6):1190-203
references: 18083107
references: Cancer. 2005 Apr 15;103(8):1670-5
references: 15751020
references: Cancer Discov. 2011 Jun;1(1):78-89
references: 22328973
references: Clin Cancer Res. 2012 Apr 1;18(7):1855-62
references: 22388515
references: J Clin Oncol. 2012 Mar 10;30(8):863-70
references: 22215748
references: J Clin Oncol. 2004 Apr 1;22(7):1180-7
references: 14981103
references: Clin Cancer Res. 2009 Dec 1;15(23):7119-23
references: 19934298
references: Eur J Pharmacol. 2008 Dec 3;599(1-3):44-53
references: 18938156
references: Oncogene. 2005 Feb 17;24(8):1477-80
references: 15608678
references: J Clin Oncol. 2012 Jan 10;30(2):134-41
references: 22025146
references: JAMA. 2012 Apr 18;307(15):1593-601
references: 22511687
references: Cancer Res. 2007 May 15;67(10):4933-9
references: 17510423
references: Cancer Res. 2005 Mar 1;65(5):1642-6
references: 15753357
references: Br J Cancer. 2007 Mar 12;96(5):808-14
references: 17299390
references: Cancer Res. 2003 Apr 1;63(7):1454-7
references: 12670889
references: Clin Cancer Res. 2003 Nov 1;9(14):5238-43
references: 14614004
references: Lung Cancer. 2004 Apr;44(1):99-110
references: 15013588
references: Nat Med. 2012 Feb 12;18(3):382-4
references: 22327622
references: J Clin Oncol. 2010 Oct 20;28(30):4609-15
references: 20855820
references: Science. 2004 Apr 23;304(5670):554
references: 15016963
references: Nature. 2002 Jun 27;417(6892):949-54
references: 12068308
references: Cancer Res. 2007 Dec 15;67(24):11924-32
references: 18089823
references: J Clin Oncol. 2010 Mar 10;28(8):1387-94
references: 20142592
references: Nat Genet. 2009 Nov;41(11):1238-42
references: 19801978
references: Lancet. 2005 Oct 29-Nov 4;366(9496):1527-37
references: 16257339
references: Lancet Oncol. 2010 Dec;11(12):1172-83
references: 21126687
references: Nat Med. 2008 Dec;14(12):1351-6
references: 19029981
references: EMBO J. 1998 Oct 15;17(20):5896-904
references: 9774334
references: Br J Cancer. 2002 May 6;86(9):1449-56
references: 11986780
references: Lung Cancer. 2012 Apr;76(1):123-7
references: 22325357
references: Mol Cancer Ther. 2012 Feb;11(2):485-91
references: 22135231
references: Nature. 2004 Sep 30;431(7008):525-6
references: 15457249
references: Nature. 2007 Aug 2;448(7153):561-6
references: 17625570
references: Oncologist. 2011;16(11):1498-507
references: 22016476
references: J Clin Oncol. 2010 Oct 1;28(28):e507-10
references: 20679607
references: J Thorac Oncol. 2012 Oct;7(10):e23-4
references: 22743296
references: Proc Natl Acad Sci U S A. 1987 Dec;84(24):9270-4
references: 2827175
references: Cancer Res. 2002 Nov 15;62(22):6451-5
references: 12438234
references: Lung Cancer. 2006 Nov;54(2):209-15
references: 16930767
references: N Engl J Med. 2001 Mar 15;344(11):783-92
references: 11248153
references: PLoS One. 2011;6(6):e20351
references: 21666749
references: J Clin Oncol. 2011 May 20;29(15):2046-51
references: 21483012
references: Clin Cancer Res. 2009 May 1;15(9):3143-9
references: 19383809
references: Clin Cancer Res. 2010 Sep 15;16(18):4647-53
references: 20534736
references: J Clin Oncol. 2012 Feb 20;30(6):647-60
references: 22271477
references: J Natl Cancer Inst. 2005 Mar 2;97(5):339-46
references: 15741570
references: Nat Med. 2012 Feb 12;18(3):375-7
references: 22327624
references: Proc Natl Acad Sci U S A. 2009 Jan 13;106(2):474-9
references: 19122144
references: Cancer Res. 2002 Dec 1;62(23):7001-3
references: 12460919
references: Cancer Res. 2006 Jul 1;66(13):6487-91
references: 16818618
references: Lancet Oncol. 2012 Mar;13(3):239-46
references: 22285168
references: Cancer Res. 2002 Dec 1;62(23):6997-7000
references: 12460918
references: N Engl J Med. 2010 Oct 28;363(18):1693-703
references: 20979469
references: N Engl J Med. 2005 Oct 20;353(16):1673-84
references: 16236738
references: Sci Transl Med. 2010 Dec 15;2(62):62ra93
references: 21160078