Evolving therapies in the treatment of hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The major etiologies and risk factors for HCC development are well defined and some of the steps involved in hepatocarcinogenesis have been elucidated in recent years. Therapeutic options that can be applied in curative or palliative intention are available and are dependent on the HCC stage. The therapeutic options fall into five main categories: (1) surgical interventions, including tumor resection and liver transplantation, (2) percutaneous interventions, including ethanol injection and radiofrequency thermal ablation, (3) transarterial interventions, including embolization and chemoembolization, (4) radiation therapy, and (5) drugs as well as gene and immune therapies. Until recently, no therapy existed for patients with advanced HCC. In 2007 a multikinase inhibitor (sorafenib) showed for the first time a significant increase in overall survival in patients with advanced HCC. Furthermore, several other agents that target different factors of hepatocarcinogenesis (eg, epidermal growth factor, insulin-like growth factors, hepatocyte growth factor, vascular endothelial growth factor, fibroblast growth factor, platelet-derived growth factor, and the transforming growth factors-alpha and -beta), have emerged and been tested in clinical trials. This review gives an overview of the current therapeutic strategies and their clinical impact.
Spangenberg
Hans Christian
HC
Department of Medicine II, University of Freiburg, D-79106 Freiburg, Germany.
Thimme
Robert
R
Blum
Hubert E
HE
Cancer. 2000 Dec 1;89(11):2266-73
11147597
Hepatology. 2005 Apr;41(4):707-16
15795889
Hepatology. 2007 Aug;46(2):430-5
17580359
Gastroenterology. 2004 Nov;127(5 Suppl 1):S56-61
15508104
Gastroenterology. 2004 Feb;126(2):460-8
14762783
Liver Transpl. 2004 Feb;10(2 Suppl 1):S115-20
14762851
World J Gastroenterol. 2008 Jan 7;14(1):1-14
18176955
J Pharmacol Exp Ther. 2005 Dec;315(3):971-9
16002463
Nature. 2004 Sep 23;431(7007):405-6
15385993
Ann Surg Oncol. 2003 May;10(4):355-62
12734082
Hepatology. 2002 Nov;36(5):1206-13
12395331
J Exp Med. 1998 Jul 20;188(2):341-50
9670046
Hepatology. 2002 Nov;36(5):1214-20
12395332
Gastroenterology. 2004 Nov;127(5 Suppl 1):S17-26
15508082
Semin Liver Dis. 2004 Feb;24(1):77-88
15085488
Gastroenterology. 2004 Nov;127(5 Suppl 1):S72-8
15508106
J Hepatol. 2006 Jan;44(1):158-66
16290309
Curr Opin Gastroenterol. 2007 May;23(3):268-74
17414842
J Exp Med. 2002 Oct 21;196(8):1105-11
12391022
Am J Gastroenterol. 2004 Aug;99(8):1477-8
15307863
Hepatology. 2004 Dec;40(6):1465-73
15565604
Mol Cancer Ther. 2006 Nov;5(11):2696-705
17121916
Curr Opin Gastroenterol. 2006 May;22(3):248-53
16550039
J Clin Oncol. 2005 Sep 20;23(27):6657-63
16170173
Lancet. 1998 Jan 17;351(9097):214-5
9449893
Gastroenterology. 2004 Nov;127(5 Suppl 1):S179-88
15508083
Cancer Res. 2006 Dec 15;66(24):11851-8
17178882
Semin Liver Dis. 1999;19(3):329-38
10518312
J Hepatol. 2005 Oct;43(4):661-9
16023762
World J Gastroenterol. 2007 Sep 7;13(33):4458-66
17724801
Am J Gastroenterol. 2002 Jan;97(1):156-61
11808941
Gastroenterology. 2004 Nov;127(5 Suppl 1):S87-96
15508108
Gastroenterology. 2004 Nov;127(5 Suppl 1):S35-50
15508101
J Clin Invest. 2007 Sep;117(9):2713-22
17717605
Am J Gastroenterol. 2007 Aug;102(8):1661-70; quiz 1660, 1671
17555459
Hepatology. 2002 Nov;36(5):1046-9
12395312
Gastroenterology. 2004 Apr;126(4):1005-14
15057740
Anticancer Res. 2005 Mar-Apr;25(2A):789-93
15868910
N Engl J Med. 1999 Mar 11;340(10):745-50
10072408
Gastroenterology. 2002 May;122(6):1609-19
12016426
Clin Cancer Res. 2004 Dec 15;10(24):8421-5
15623621
Cancer. 2002 Mar 15;94(6):1760-9
11920539
J Natl Cancer Inst. 2006 Aug 16;98(16):1142-57
16912267
N Engl J Med. 2002 Jul 18;347(3):168-74
12124405
Hepatology. 2004 Dec;40(6):1396-405
15565571
J Clin Oncol. 2006 Jun 20;24(18):2866-72
16717293
JAMA. 2006 Jan 4;295(1):65-73
16391218
Br J Cancer. 2005 Jun;92 Suppl 1:S14-20
15928653
Cancer. 2007 Sep 1;110(5):1059-67
17623837
J Clin Oncol. 2023 Oct 20;41(30):4714-4720
37847995
Front Biosci. 2002 Jul 1;7:e301-14
12086922
Hepatology. 2004 Aug;40(2):276-83
15368430
World J Gastroenterol. 2004 Mar 1;10(5):643-8
14991930
Hepatology. 1996 Jul;24(1):198-205
8707262
Transplantation. 2007 Feb 27;83(4):425-32
17318075
Clin Cancer Res. 2003 Jan;9(1):327-37
12538485
J Clin Oncol. 2006 Sep 10;24(26):4293-300
16908937
Eur J Cancer. 2002 Sep;38 Suppl 5:S3-10
12528767
Histol Histopathol. 2007 Mar;22(3):285-9
17163402
Cancer. 2007 Aug 1;110(3):581-9
17583545
Semin Liver Dis. 1999;19(3):235-42
10518303
J Hepatol. 1999 Jul;31(1):133-41
10424293
Lancet. 1997 Oct 18;350(9085):1142-3
9343506
Gastroenterology. 2007 Jun;132(7):2557-76
17570226
Ann Intern Med. 2003 Nov 18;139(10):817-23
14623619
Prostate. 2006 Dec 1;66(16):1788-98
17013882
J Hepatol. 2007 Dec;47(6):860-7
17935820
Cancer. 2003 Jun 15;97(12):3036-43
12784339
J Hepatol. 2005 Feb;42(2):218-24
15664247
Semin Oncol. 2006 Aug;33(4):392-406
16890795
Cancer. 2008 Jan 15;112(2):250-9
18041064
N Engl J Med. 2003 Apr 24;348(17):1625-38
12711737
Hepatology. 2007 Nov;46(5):1350-6
17680653
Hepatology. 2005 Nov;42(5):1208-36
16250051
Mech Dev. 2003 Jan;120(1):19-33
12490293
Gastroenterology. 2004 Nov;127(5 Suppl 1):S126-32
15508076
J Hepatol. 2007 May;46(5):840-8
17321636
Cancer. 1985 Aug 15;56(4):918-28
2990661
Hepatology. 2007 Nov;46(5):1357-64
17657816
Nature. 2004 Sep 23;431(7007):461-6
15329734
Biochem Pharmacol. 2005 Nov 25;70(11):1568-78
16226226
J Hepatol. 2000;32(1 Suppl):225-37
10728807
Hepatology. 2002 Mar;35(3):519-24
11870363
Essays Biochem. 2005;41:205-18
16250907
Gastroenterology. 2004 Nov;127(5 Suppl 1):S27-34
15508094
Cancer Res. 2004 Oct 1;64(19):7099-109
15466206
J Hepatol. 2001 Sep;35(3):421-30
11592607
Gastroenterology. 2004 Jan;126(1):102-10
14699492
Science. 2007 Jul 6;317(5834):121-4
17615358
J Hepatol. 2007 Nov;47(5):684-90
17854945
Lancet. 2003 Dec 6;362(9399):1907-17
14667750
Proc Natl Acad Sci U S A. 2005 Mar 1;102(9):3389-94
15728360
Gastroenterology. 2004 Nov;127(5 Suppl 1):S97-103
15508109
Br J Surg. 2004 Oct;91(10):1354-60
15376182
Hepatology. 2003 Mar;37(3):520-7
12601348
Anticancer Drugs. 2006 Aug;17(7):783-95
16926628