Targeted therapies for hepatocellular carcinoma - PubMed (original) (raw)

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Targeted therapies for hepatocellular carcinoma

Augusto Villanueva et al. Gastroenterology. 2011 May.

Abstract

Unlike most solid tumors, the incidence and mortality of hepatocellular carcinoma (HCC) have increased in the United States and Europe in the past decade. Most patients are diagnosed at advanced stages, so there is an urgent need for new systemic therapies. Sorafenib, a tyrosine kinase inhibitor (TKI), has shown clinical efficacy in patients with HCC. Studies in patients with lung, breast, or colorectal cancers have indicated that the genetic heterogeneity of cancer cells within a tumor affect its response to therapeutics designed to target specific molecules. When tumor progression requires alterations in specific oncogenes (oncogene addiction), drugs that selectively block their products might slow tumor growth. However, no specific oncogene addictions are yet known to be implicated in HCC progression, so it is important to improve our understanding of its molecular pathogenesis. There are currently many clinical trials evaluating TKIs for HCC, including those tested in combination with (eg, erlotinib) or compared with (eg, linifanib) sorafenib as a first-line therapy. For patients who do not respond or are intolerant to sorafenib, TKIs such as brivanib, everolimus, and monoclonal antibodies (eg, ramucirumab) are being tested as second-line therapies. There are early stage trials investigating the efficacy for up to 60 reagents for HCC. Together, these studies might change the management strategy for HCC, and combination therapies might be developed for patients with advanced HCC. Identification of oncogenes that mediate tumor progression, and trials that monitor their products as biomarkers, might lead to personalized therapy; reagents that interfere with signaling pathways required for HCC progression might be used to treat selected populations, and thereby maximize the efficacy and cost benefit.

Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

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Figures

Figure 1

Figure 1. Targeted and Systemic Therapies for CRC

In a trial of cetuximab as a second-line therapy for patients with CRC, those with tumors that expressed wild-type KRAS mutation had longer survival times than patients whose tumor cells had KRAS mutations (right panel). Data were obtained from 2 studies analyzing a total of 572 CRC patients, . Survival trends for patients with advanced CRC from 1990 to 2005, based on treatment. Those that received a combination of chemotherapy and targeted therapy (an anti-angiogenic agent), and the longest survival times. IFL, irinotecan, bolus of 5-fluoruoracil, and leucovorin; FOLFOX, 5-fluoruracil, leucovorin, and oxaliplatin; FOLFIRI, irinotecan, infusion of 5-fluoruoracil, and leucovorin.

Figure 2

Figure 2

Individualizing therapy for patients with HCC. Therapeutics might be developed to target factors that contribute to progression of most tumor types (therapeutic approach) and factors required for progression of HCC, specifically (oncogene addiction). This approach is used to treat patients with CRC and other types of cancer.

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