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Targeted Therapies for Hepatocellular Carcinoma

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Hepatocellular Carcinoma

Part of the book series: Current Clinical Oncology ((CCO))

Abstract

The years of fundamental cancer biology research is now starting to pay clinical dividends, with the identification of key enzymatic steps in the growth control and angiogenesis pathways, resulting in specific chemical inhibitors and antibodies to several of the involved kinases. This has led to the FDA approval of sorafenib, a multityrosine kinase inhibitor that enhanced survival of patients with advanced hepatocellular carcinoma (HCC). Within the last 5 years, other novel, non-chemotherapy agents, evaluated as first-line agents (i.e., sunitinib, linifanib, brivanib, erlotinib plus sorafenib) or second-line agents (brivanib, everolimus, ramucirumab) in phase III studies, failed to achieve their primary endpoint (overall survival). To improve outcomes for HCC, molecular pathways leading to the pathogenesis of HCC need to be further elucidated, and biomarkers should be evaluated and integrated into clinical studies. Notably, a phase II study suggests biomarkers may potentially play a role in the selection of patients responsive to therapy. In a phase II study evaluating placebo versus tivantinib, a c-MET tyrosine kinase inhibitor, patients with MET-high tumors were responsive to tivantinib and had significantly improved median overall survival with tivantinib versus placebo. Patients with HCC and diagnostically c-MET-high tumors are prospectively being recruited into phase III studies to further evaluate the use of a biomarker to select patients and the efficacy and safety of tivantinib. This may potentially mark the next era of management of HCC-personalized medicine.

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Authors and Affiliations

  1. New York, NY, USA

    Susan Kralian

  2. Izmir Biomedicine and Genome Center, Dokuz Eylül University, Izmir, Turkey

    Brian I. Carr

  3. Lusaka Apex Medical University, Lusaka, Zambia

    Brian I. Carr

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    Brian I. Carr

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Kralian, S., Carr, B.I. (2016). Targeted Therapies for Hepatocellular Carcinoma. In: Carr, B. (eds) Hepatocellular Carcinoma. Current Clinical Oncology. Springer, Cham. https://doi.org/10.1007/978-3-319-34214-6_34

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