title: ALK and NSCLC: Targeted therapy with ALK inhibitors.
abstract: For many years treatment for advanced or metastatic non-small cell lung cancer (NSCLC) has employed chemotherapy regimens for patient care, with limited effect. Five-year survival rates for these patients are not encouraging. However, for a subgroup of these patients, there have been radical changes over recent years. Our understanding of the basic pathology behind NSCLC at the molecular level has offered up a host of new molecularly targeted therapies, which are revolutionizing this area of cancer care. Results from recent clinical trials provide hope for NSCLC patients harboring oncogenic translocations involving the anaplastic lymphoma kinase (ALK) receptor tyrosine kinase. Just as inhibition of the breakpoint cluster region-ABL complex has changed the face of chronic myeloid leukemia diagnosis, oncogenic ALK fusions offer a step forward in the diagnosis and treatment of ALK-positive NSCLC. This article discusses the current knowledge and potential implications concerning ALK inhibitors and NSCLC.
authors.affiliation: Department of Molecular Biology, Umeå University, Umeå S-901 87 Sweden.
authors.forename: Bengt
authors.initials: B
authors.lastname: Hallberg
authors.forename: Ruth H
authors.initials: RH
authors.lastname: Palmer
references.citation: Cancer Res. 2010 Dec 1;70(23):9827-36
references.pmid: 20952506
references.citation: J Clin Oncol. 2009 Sep 10;27(26):4247-53
references.pmid: 19667264
references.citation: Biochemistry. 2010 Aug 17;49(32):6813-25
references.pmid: 20695522
references.citation: Cancer Res. 2007 Dec 15;67(24):11924-32
references.pmid: 18089823
references.citation: Science. 2004 Jun 4;304(5676):1497-500
references.pmid: 15118125
references.citation: Bioorg Med Chem. 2009 May 1;17(9):3308-16
references.pmid: 19362847
references.citation: Int J Clin Oncol. 2011 Aug;16(4):287-93
references.pmid: 21562939
references.citation: Science. 2005 Oct 28;310(5748):644-8
references.pmid: 16254181
references.citation: Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):270-5
references.pmid: 17185414
references.citation: J Clin Oncol. 2007 Feb 10;25(5):472-8
references.pmid: 17290054
references.citation: Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):2070-5
references.pmid: 18227510
references.citation: Neoplasia. 2008 Mar;10(3):298-302
references.pmid: 18320074
references.citation: Nature. 2008 Oct 16;455(7215):930-5
references.pmid: 18724359
references.citation: Oncogene. 1994 Jun;9(6):1567-74
references.pmid: 8183550
references.citation: Cancer Res. 2008 May 1;68(9):3389-95
references.pmid: 18451166
references.citation: Cell. 2007 Mar 9;128(5):961-75
references.pmid: 17350579
references.citation: Med Res Rev. 2008 May;28(3):372-412
references.pmid: 17694547
references.citation: Cell. 2007 Dec 14;131(6):1190-203
references.pmid: 18083107
references.citation: Bioorg Med Chem. 2010 Jun 15;18(12):4351-62
references.pmid: 20483621
references.citation: Nature. 2008 Oct 16;455(7215):975-8
references.pmid: 18923525
references.citation: N Engl J Med. 2010 Oct 28;363(18):1760-2
references.pmid: 20979477
references.citation: J Mol Med (Berl). 2007 Aug;85(8):863-75
references.pmid: 17318615
references.citation: Nature. 2008 Oct 16;455(7215):971-4
references.pmid: 18923524
references.citation: World J Gastroenterol. 2006 Nov 28;12(44):7104-12
references.pmid: 17131471
references.citation: Br J Cancer. 2008 May 6;98(9):1536-9
references.pmid: 18414414
references.citation: Bioorg Med Chem. 2011 May 15;19(10):3086-95
references.pmid: 21515061
references.citation: Clin Cancer Res. 2008 Jul 1;14(13):4275-83
references.pmid: 18594010
references.citation: J Thorac Oncol. 2008 Jan;3(1):13-7
references.pmid: 18166835
references.citation: Neuropsychopharmacology. 2008 Feb;33(3):685-700
references.pmid: 17487225
references.citation: Proc Natl Acad Sci U S A. 2011 May 3;108(18):7535-40
references.pmid: 21502504
references.citation: Am J Pathol. 2009 Feb;174(2):661-70
references.pmid: 19147828
references.citation: Gene Expr Patterns. 2006 Jun;6(5):448-61
references.pmid: 16458083
references.citation: Expert Opin Ther Pat. 2010 Dec;20(12):1653-81
references.pmid: 20961208
references.citation: Cancer Res. 2011 Jul 15;71(14):4920-31
references.pmid: 21613408
references.citation: Biochem J. 2008 Dec 1;416(2):153-9
references.pmid: 18990089
references.citation: N Engl J Med. 2010 Oct 28;363(18):1734-9
references.pmid: 20979473
references.citation: Int J Clin Oncol. 2011 Aug;16(4):294-305
references.pmid: 21655907
references.citation: Cancer Res. 2011 Jul 1;71(13):4403-11
references.pmid: 21596819
references.citation: N Engl J Med. 2011 Mar 10;364(10):947-55
references.pmid: 21388312
references.citation: J Mol Endocrinol. 2011 Jul 04;47(1):R11-23
references.pmid: 21502284
references.citation: Nat Rev Cancer. 2008 Jan;8(1):11-23
references.pmid: 18097461
references.citation: Nature. 2008 Oct 16;455(7215):967-70
references.pmid: 18923523
references.citation: Mol Cancer Ther. 2009 Oct;8(10):2811-20
references.pmid: 19825801
references.citation: Cancer. 2011 Jun 15;117(12):2709-18
references.pmid: 21656749
references.citation: J Clin Oncol. 2010 Nov 20;28(33):4953-60
references.pmid: 20940188
references.citation: Cancer Cell. 2011 May 17;19(5):679-90
references.pmid: 21575866
references.citation: Mol Cancer Ther. 2007 Dec;6(12 Pt 1):3314-22
references.pmid: 18089725
references.citation: Cancer Res. 2008 Jul 1;68(13):4971-6
references.pmid: 18593892
references.citation: Biochem J. 2010 Sep 15;430(3):425-37
references.pmid: 20632993
references.citation: Nature. 2007 Aug 2;448(7153):561-6
references.pmid: 17625570
references.citation: Clin Cancer Res. 2009 Aug 15;15(16):5216-23
references.pmid: 19671850
references.citation: Anticancer Drugs. 2009 Jun;20(5):364-72
references.pmid: 19322071
references.citation: Biochem J. 2009 May 27;420(3):345-61
references.pmid: 19459784
references.citation: Science. 1994 Mar 4;263(5151):1281-4
references.pmid: 8122112
references.citation: Lung Cancer. 2008 Aug;61(2):163-9
references.pmid: 18242762
references.citation: Clin Cancer Res. 2009 May 1;15(9):3143-9
references.pmid: 19383809
references.citation: N Engl J Med. 2004 May 20;350(21):2129-39
references.pmid: 15118073
references.citation: Proc Natl Acad Sci U S A. 2008 Dec 16;105(50):19893-7
references.pmid: 19064915
references.citation: Cancer. 2009 Apr 15;115(8):1723-33
references.pmid: 19170230
references.citation: Eur J Cancer. 2010 Jul;46(10):1773-80
references.pmid: 20418096
references.citation: N Engl J Med. 2010 Oct 28;363(18):1693-703
references.pmid: 20979469