title: Targeting the HGF/c-MET pathway in hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) is a significant cause of cancer-related morbidity and mortality worldwide. Despite improvements in local therapies, including surgical resection, liver transplantation, and transarterial embolization, the prognosis remains poor for the majority of patients who develop recurrence or present with advanced disease. Systemic therapy with the tyrosine kinase inhibitor sorafenib represents a milestone in advanced HCC but provides a limited survival benefit. Ongoing efforts to study hepatocarcinogenesis have identified an important role for c-MET signaling in the promotion of tumor growth, angiogenesis, and metastasis. In this review, we summarize the preclinical data from human tissue, cell lines, and animal models that implicate c-MET in the pathogenesis of HCC. We also evaluate potential biomarkers that may estimate prognosis or predict response to c-MET inhibitors for more rational clinical trial design. Finally, we discuss the latest clinical trials of c-MET inhibitors in advanced HCC.
authors: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts 02114, USA.
authors: Lipika
authors: L
authors: Goyal
authors: Mandar D
authors: MD
authors: Muzumdar
authors: Andrew X
authors: AX
authors: Zhu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism; D002986:Clinical Trials as Topic; D017228:Hepatocyte Growth Factor / Q000502:physiology*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D058990:Molecular Targeted Therapy; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; C066855:HGF protein, human; D017228:Hepatocyte Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
references: Jpn J Cancer Res. 1995 Aug;86(8):718-23
references: 7559093
references: Oncogene. 2002 Feb 21;21(9):1335-45
references: 11857077
references: Nature. 1995 Aug 31;376(6543):768-71
references: 7651534
references: Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):373-7
references: 1309612
references: J Gastrointest Surg. 2008 Feb;12(2):327-37
references: 17943391
references: Int J Cancer. 2000 Sep 1;87(5):644-9
references: 10925356
references: Mol Cancer Ther. 2010 Jun;9(6):1544-53
references: 20484018
references: Nature. 1984 Sep 6-11;311(5981):29-33
references: 6590967
references: J Hepatol. 1996 Mar;24(3):286-92
references: 8778194
references: Hepatology. 1996 Jul;24(1):60-4
references: 8707284
references: Hepatology. 1994 Nov;20(5):1231-6
references: 7927256
references: Biol Cell. 2009 Sep;101(9):525-39
references: 19281453
references: N Engl J Med. 2008 Jul 24;359(4):378-90
references: 18650514
references: Mol Cancer Ther. 2011 Dec;10(12):2298-308
references: 21926191
references: Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1937-41
references: 7680481
references: Cancer Res. 1999 Jan 15;59(2):307-10
references: 9927037
references: Clin Cancer Res. 1997 Jul;3(7):1059-66
references: 9815784
references: Cancer Res. 2011 Jul 15;71(14):4758-68
references: 21613405
references: Carcinogenesis. 1995 Apr;16(4):841-3
references: 7728965
references: Lancet Oncol. 2009 Jan;10(1):25-34
references: 19095497
references: Int J Clin Oncol. 2013 Apr;18(2):207-13
references: 22218908
references: Nature. 1995 Feb 23;373(6516):699-702
references: 7854452
references: J Biol Chem. 2005 Feb 25;280(8):6409-15
references: 15582995
references: Hepatology. 1997 Jul;26(1):59-66
references: 9214452
references: Nat Rev Cancer. 2012 Jan 24;12(2):89-103
references: 22270953
references: Science. 1991 Feb 15;251(4995):802-4
references: 1846706
references: Hepatology. 1994 Apr;19(4):962-72
references: 8138271
references: J Gastrointest Surg. 2009 Feb;13(2):325-33
references: 18846405
references: Hepatology. 1994 Jan;19(1):88-91
references: 8276372
references: J Clin Invest. 2006 Jun;116(6):1582-95
references: 16710476
references: Clin Cancer Res. 2012 Apr 15;18(8):2290-300
references: 22374331
references: Gastroenterology. 1998 Apr;114(4):775-81
references: 9516398
references: Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14417-22
references: 9826715
references: Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10608-13
references: 15249655
references: J Hepatol. 2006 Oct;45(4):529-38
references: 16879891
references: J Hepatol. 2012 Apr;56(4):908-43
references: 22424438
references: Nature. 1989 Nov 23;342(6248):440-3
references: 2531289
references: BMC Cancer. 2009 May 29;9:165
references: 19476653
references: Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12718-23
references: 14555767
references: J Surg Res. 2010 Aug;162(2):231-8
references: 19765730
references: Oncogene. 2002 Mar 14;21(12):1791-9
references: 11896611
references: Int J Cancer. 2010 Dec 15;127(12):2893-917
references: 21351269
references: Hepatology. 1997 Mar;25(3):619-23
references: 9049208
references: Nature. 1987 May 21-27;327(6119):239-42
references: 2952888
references: Angiogenesis. 2012 Mar;15(1):59-70
references: 22187171
references: Cancer Res. 2009 Oct 15;69(20):8009-16
references: 19808973
references: Mol Cancer Ther. 2005 Oct;4(10):1577-84
references: 16227408
references: FEBS Lett. 1991 Oct 21;291(2):229-32
references: 1657643
references: Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14771-6
references: 17785413
references: Cancer Cell. 2003 Apr;3(4):347-61
references: 12726861
references: Hepatology. 2011 Sep 2;54(3):879-89
references: 21618573
references: J Hepatol. 1994 Aug;21(2):227-34
references: 7989714
references: Dig Liver Dis. 2006 Jul;38(7):490-7
references: 16627020
references: Int J Oncol. 2007 Aug;31(2):451-60
references: 17611703
references: Hepatology. 1995 Jan;21(1):106-12
references: 7806142
references: Oncogene. 1994 Jul;9(7):2019-27
references: 8208547
references: J Cell Biol. 2001 May 28;153(5):1023-34
references: 11381087
references: J Natl Cancer Inst. 2008 May 21;100(10):698-711
references: 18477802
references: J Gastroenterol. 2004 Dec;39(12):1182-8
references: 15622483
references: Mol Cell Biol. 1993 Nov;13(11):6711-22
references: 8413267
references: Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9577-82
references: 8790372
references: Cell Growth Differ. 1996 Nov;7(11):1513-23
references: 8930401
references: Biochem Biophys Res Commun. 1984 Aug 16;122(3):1450-9
references: 6477569
references: Mol Carcinog. 2003 Mar;36(3):130-41
references: 12619035