Systemic treatment and targeted therapy in patients with advanced hepatocellular carcinoma

Abstract

Background:Advanced hepatocellular carcinoma (HCC) is a malignancy of global importance: it is the sixth most common cancer and the third most common cause of cancer-related mortality worldwide. Despite decades of efforts by many investigators, systemic chemotherapy or hormone therapy has failed to demonstrate improved survival in patients with HCC.. Ongoing studies are evaluating the efficacy and tolerability of combining Sorafenib with erlotinib and other targeted agents or chemotherapy.Aims:On the basis of placebo-controlled, randomized phase III trials, Sorafenib has shown improved survival benefits in advanced HCC and has set a new standard for future clinical trials. The successful clinical development of Sorafenib in HCC has ushered in the era of molecularly targeted agents in this disease, which is discussed in this educational review.Material and Methods:Many molecularly targeted agents that inhibit angiogenesis, epidermal growth factor receptor, and mammalian target of rapamycin are at different stages of clinical development in advanced HCC. Future research should continue to unravel the mechanism of hepatocarcinogenesis and to identify key relevant molecular targets for therapeutic intervention. Identification and validation of potential surrogate and predictive biomarkers hold promise to individualize patients’ treatment to maximize clinical benefit and minimize the toxicity and cost of targeted agents.Results:Systemic therapy with various classes of agents, including hormone and cytotoxic agents, has provided no or marginal benefits. Improved understanding of the mechanism of hepatocarcinogenesis, coupled with the arrival of many newly developed molecularly targeted agents, has provided the unique opportunity to study some of these novel agents in advanced HCC.Conclusions:The demonstration of improved survival benefits by Sorafenib in advanced HCC has ushered in the era of molecular-targeted therapy in this disease, with many agents undergoing active clinical development.

SEARCH: A Phase III, Randomized, Double-Blind, Placebo-Controlled Trial of Sorafenib Plus Erlotinib in Patients With Advanced Hepatocellular Carcinoma

“…6,7 Other targeted agents, alone or combined with sorafenib, have been tested in patients with HCC. 8,9 The epidermal growth factor receptor (EGFR) pathway has been implicated in the pathogenesis of HCC. 10,11 EGFR activation may interfere with HCC response to sorafenib, [11][12][13] suggesting that EGFR inhibition may enhance tumor response.…”

Overexpression of Yes‐associated protein and its association with clinicopathological features of hepatocellular carcinoma: A meta‐analysis

“…Although multiple therapeutic modalities are available to treat HCC, mortality is still unacceptably high. Recently, research on tumour signal transduction pathways have revealed important pathway proteins that could be exploited for treatment targets, and these approaches have increased patient survival …”

Circulating B7-H4 in serum predicts prognosis in patients with hepatocellular carcinoma

“…In addition, some novel treatment strategies such as molecular targeted therapy and gene therapy have also been developed to fight against HCC (el Tazi et al, 2011;Duan et al, 2013). However, prognosis of many HCC patients remains poor.…”