Molecular targeted therapies in hepatocellular carcinoma: From pre-clinical models to clinical trials

Journal of Hepatology

Volumn 49, Issue 1, 2008, Pages 1-5

  Newell, Pippa ^a   Villanueva, Augusto ^b   Llovet, Josep M ^a,b  

^a MOUNT SINAI MEDICAL CENTER   (United States)

^b INSTITUT D INVESTIGACIONS BIOMÈDIQUES AUGUST PI I SUNYER IDIBAPS   (Spain)

Author keywords

Clinical trials; Combination therapy; Liver cancer; Mouse models; Signaling pathway; Targeted therapy

Indexed keywords

BEVACIZUMAB; BORTEZOMIB; CETUXIMAB; CYTOTOXIC AGENT; ERLOTINIB; EVEROLIMUS; GEFITINIB; RAPAMYCIN; RAPAMYCIN DERIVATIVE; SORAFENIB; SUNITINIB; TEMSIROLIMUS; TYROSINE KINASE RECEPTOR; VASCULOTROPIN;

BREAST CANCER; CANCER INHIBITION; CANCER SURVIVAL; CANCER THERAPY; CLINICAL TRIAL; COLON CANCER; DRUG EFFICACY; DRUG POTENCY; DRUG SCREENING; EDITORIAL; EXPERIMENTAL MODEL; EXPERIMENTAL MOUSE; GENETIC ENGINEERING; HUMAN; LIVER CELL CARCINOMA; LIVER METASTASIS; LUNG NON SMALL CELL CANCER; MOLECULAR THERAPY; NONHUMAN; OVARY CANCER; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; TUMOR XENOGRAFT; XENOGRAFT;

ANGIOGENESIS INHIBITORS; ANIMALS; ANTINEOPLASTIC AGENTS; CARCINOMA, HEPATOCELLULAR; CLINICAL TRIALS AS TOPIC; HUMANS; LIVER NEOPLASMS;

EID: 44749089874     PISSN: 01688278     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jhep.2008.04.006     Document Type: Editorial

References (48)

1. Farazi P.A., and DePinho R.A. Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer 6 (2006) 674-687
2. Dancey J.E., and Chen H.X. Strategies for optimizing combinations of molecularly targeted anticancer agents. Nat Rev Drug Discov 5 (2006) 649-659
3. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Raoul J, Zeuzem S, et al. for the SHARP Investigators. Sorafenib improves survival in advanced hepatocellular carcinoma (HCC): results of a phase III randomized placebo-controlled trial. J Clin Oncol 2007;25: LBA1.
4. Chiang D., Villanueva A., Peix J., Newell P., Wurmbach E., Donovan D., et al. Integrative genomic classification of hepatitis C virus positive hepatocellular carcinoma. Hepatology 46 Suppl (2007) Abstract #657
5. Villanueva A., Newell P., Chiang D.Y., Friedman S.L., and Llovet J.M. Genomics and signaling pathways in hepatocellular carcinoma. Semin Liver Dis 27 (2007) 55-76
6. Semela D., and Dufour J.F. Angiogenesis and hepatocellular carcinoma. J Hepatol 41 (2004) 864-880
7. Hussain S.P., Schwank J., Staib F., Wang X.W., and Harris C.C. TP53 mutations and hepatocellular carcinoma: insights into the etiology and pathogenesis of liver cancer. Oncogene 26 (2007) 2166-2176
8. Satyanarayana A., Manns M.P., and Rudolph K.L. Telomeres and telomerase: a dual role in hepatocarcinogenesis. Hepatology 40 (2004) 276-283
9. Calvisi D.F., Ladu S., Gorden A., Farina M., Conner E.A., Lee J.S., et al. Ubiquitous activation of Ras and Jak/Stat pathways in human HCC. Gastroenterology 130 (2006) 1117-1128
10. Lee J.S., Heo J., Libbrecht L., Chu I.S., Kaposi-Novak P., Calvisi D.F., et al. A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells. Nat Med 12 (2006) 410-416
11. Boyault S., Rickman D.S., de Reynies A., Balabaud C., Rebouissou S., Jeannot E., et al. Transcriptome classification of HCC is related to gene alterations and to new therapeutic targets. Hepatology 45 (2007) 42-52
12. Buendia M.A. Genetics of hepatocellular carcinoma. Semin Cancer Biol 10 (2000) 185-200
13. Llovet J, Bruix J. Molecular targeted therapies in HCC. Hepatology 2008, in press.
14. Rygaard J., and Povlsen C.O. Heterotransplantation of a human malignant tumour to "Nude" mice. Acta Pathol Microbiol Scand 77 (1969) 758-760
15. Frese K.K., and Tuveson D.A. Maximizing mouse cancer models. Nat Rev Cancer 7 (2007) 645-658
16. Newell P., Villanueva A., Friedman S.L., Koike K., and Llovet J.M. Experimental models of hepatocellular carcinoma. J Hepatol 48 (2008) 858-879
17. Huynh H., Soo K.C., Chow P.K., Panasci L., and Tran E. Xenografts of human hepatocellular carcinoma: a useful model for testing drugs. Clin Cancer Res 12 (2006) 4306-4314
18. Hoffman R.M. Orthotopic metastatic (MetaMouse) models for discovery and development of novel chemotherapy. Methods Mol Med 111 (2005) 297-322
19. Kornek M., Raskopf E., Tolba R., Becker U., Klockner M., Sauerbruch T., et al. Accelerated orthotopic hepatocellular carcinomas growth is linked to increased expression of pro-angiogenic and prometastatic factors in murine liver fibrosis. Liver Int 28 (2008) 509-518
20. Lee J.S., Chu I.S., Mikaelyan A., Calvisi D.F., Heo J., Reddy J.K., et al. Application of comparative functional genomics to identify best-fit mouse models to study human cancer. Nat Genet 36 (2004) 1306-1311
21. Campbell J.S., Hughes S.D., Gilbertson D.G., Palmer T.E., Holdren M.S., Haran A.C., et al. Platelet-derived growth factor C induces liver fibrosis, steatosis, and hepatocellular carcinoma. Proc Natl Acad Sci USA 102 (2005) 3389-3394
22. Thompson M.D., and Monga S.P. WNT/beta-catenin signaling in liver health and disease. Hepatology 45 (2007) 1298-1305
23. Johnson J.I., Decker S., Zaharevitz D., Rubinstein L.V., Venditti J.M., Schepartz S., et al. Relationships between drug activity in NCI preclinical in vitro and in vivo models and early clinical trials. Br J Cancer 84 (2001) 1424-1431
24. Voskoglou-Nomikos T., Pater J.L., and Seymour L. Clinical predictive value of the in vitro cell line, human xenograft, and mouse allograft preclinical cancer models. Clin Cancer Res 9 (2003) 4227-4239
25. Kerbel R.S. Human tumor xenografts as predictive preclinical models for anticancer drug activity in humans: better than commonly perceived-but they can be improved. Cancer Biol Ther 2 (2003) S134-S139
26. Chang Y.S., Adnane J., Trail P.A., Levy J., Henderson A., Xue D., et al. Sorafenib (BAY 43-9006) inhibits tumor growth and vascularization and induces tumor apoptosis and hypoxia in RCC xenograft models. Cancer Chemother Pharmacol 59 (2007) 561-574
27. Liu L., Cao Y., Chen C., Zhang X., McNabola A., Wilkie D., et al. Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5. Cancer Res 66 (2006) 11851-11858
28. Wilhelm S.M., Carter C., Tang L., Wilkie D., McNabola A., Rong H., et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 64 (2004) 7099-7109
29. Zhu A.X. Development of sorafenib and other molecularly targeted agents in hepatocellular carcinoma. Cancer 112 (2008) 250-259
30. Mendel D.B., Laird A.D., Xin X., Louie S.G., Christensen J.G., Li G., et al. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res 9 (2003) 327-337
31. Bergers G., Song S., Meyer-Morse N., Bergsland E., and Hanahan D. Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. J Clin Invest 111 (2003) 1287-1295
32. Zhu A.X., Sahani D.V., di Tomaso E., Duda D., Sindhwani V., Yoon S.S., et al. A phase II study of sunitinib in patients with advanced hepatocellular carcinoma. J Clin Oncol 25 (2007) 4637
33. Faivre S., Delbaldo C., Vera K., Robert C., Lozahic S., Lassau N., et al. Safety, pharmacokinetic, and antitumor activity of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer. J Clin Oncol 24 (2006) 25-35
34. Rini B.I. Temsirolimus, an inhibitor of mammalian target of rapamycin. Clin Cancer Res 14 (2008) 1286-1290
35. Seeliger H., Guba M., Kleespies A., Jauch K.W., and Bruns C.J. Role of mTOR in solid tumor systems: a therapeutical target against primary tumor growth, metastases, and angiogenesis. Cancer Metastasis Rev 26 (2007) 611-621
36. Sieghart W., Fuereder T., Schmid K., Cejka D., Werzowa J., Wrba F., et al. Mammalian target of rapamycin pathway activity in hepatocellular carcinomas of patients undergoing liver transplantation. Transplantation 83 (2007) 425-432
37. Hudes G., Carducci M., Tomczak P., Dutcher J., Figlin R., Kapoor A., et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 356 (2007) 2271-2281
38. Huether A., Hopfner M., Sutter A.P., Schuppan D., and Scherubl H. Erlotinib induces cell cycle arrest and apoptosis in hepatocellular cancer cells and enhances chemosensitivity towards cytostatics. J Hepatol 43 (2005) 661-669
39. Philip P.A., Mahoney M.R., Allmer C., Thomas J., Pitot H.C., Kim G., et al. Phase II study of Erlotinib (OSI-774) in patients with advanced hepatocellular cancer. J Clin Oncol 23 (2005) 6657-6663
40. Thomas M.B., Iwasaki M., Glover K., and Abbruzzese J.L. The combination of bevacizumab (B) and erlotinib (E) shows significant biological activity in patients with advanced hepatocellular carcinoma. J Clin Oncol 25 (2007) 4567
41. Schiffer E., Housset C., Cacheux W., Wendum D., Desbois-Mouthon C., Rey C., et al. Gefitinib, an EGFR inhibitor, prevents hepatocellular carcinoma development in the rat liver with cirrhosis. Hepatology 41 (2005) 307-314
42. O'Dwyer P.J., Levy D.E., Kauh J.S., Fitzgerald D.B., and Benson III A.B. Gefitinib in advanced unresectable hepatocellular carcinoma: results from the Eastern Cooperative Oncology Group's Study E1203. J Clin Oncol 24 (2006) 4143
43. Huether A., Hopfner M., Baradari V., Schuppan D., and Scherubl H. EGFR blockade by cetuximab alone or as combination therapy for growth control of hepatocellular cancer. Biochem Pharmacol 70 (2005) 1568-1578
44. Gruenwald V., Wilkens L., Gebel M., Greten T.F., Kubicka S., Ganser A., et al. A phase II open-label study of cetuximab in unresectable hepatocellular carcinoma: final results. J Clin Oncol 25 (2007) 4598
45. Malka D.C., Dromain C., Farace F., Horn S., Pignon J., Ducreux M., et al. Bevacizumab in patients with advanced hepatocellular carcinoma (HCC): preliminary results of a phase II study with circulating endothelial cell (CEC) monitoring. J Clin Oncol 25 (2007) 4570
46. Schwartz J.D., and Lehrer D. Bevacizumab in unresectable hepatocellular carcinoma (HCC) for patients without metastasis and without invasion of the portal vein. J Clin Oncol 25 (2006) 4144
47. Kelland L.R. Of mice and men: values and liabilities of the athymic nude mouse model in anticancer drug development. Eur J Cancer 40 (2004) 827-836
48. Llovet JM, Di Bisceglie A, Bruix J, Kramer B, Lencioni R, Zhu A, et al. Design and end-points of clinical trials in HCC. J Natl Cancer Inst 2008, in press.