Hepatocellular Carcinoma: Past and Future of Molecular Target Therapy

Abstract

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer related mortality worldwide. The incidence of HCC has been increasing annually. Viral infection, alcohol usage, and other causes of cirrhosis have been identified as major risk factors for HCC development. The underlying pathogenesis has not been as well defined. There have been multiple hypotheses to the specific mechanisms of hepatocarcinogenesis and they share the common theme of chronic inflammation, increase oxidative stress, and genomic alteration. Therapeutic options of HCC have been primarily local and/or regional including transplantation, resection, and radial frequency ablation, chemoembolization or radio-embolization. For unresectable or metastatic disease, the options are limited. Conventional chemotherapeutic options have been noted to have limited benefit. Sorafenib has been the one and only systemic therapy which has demonstrated modest overall survival benefit. This has led to more extensive research with focus on targeted therapy. Numerous pre-clinical and early phase clinical studies have been noted but failed to show efficacy in later phase clinical trials. In an effort to identify new potential therapeutic options, new understanding of underlying pathways to hepatocarcinogenesis should be one of the main focuses. This leads to development of more molecularly targeted agents to specific pathways, and immunotherapy. This article provides a review of major studies of molecular targeted agents which attempts to target these specific pathways in HCC.

Cancer stem cells in hepatocellular carcinoma: an overview and promising therapeutic strategies

“…Sorafenib targets cell surface tyrosine kinase receptors such as vascular endothelial growth factor receptor, platelet-derived growth factor receptor and epidermal growth factor receptor (EGFR) as well as serine/tyrosine kinases including Raf, FMS-like tyrosine kinase-3 (Flt-3) and c-kit. 55 An in vitro study demonstrated that sorafenib could efficiently reduce cell viability and induce apoptosis in HCC cell lines. 7 However, advanced HCC patients only had a survival benefit of 3 months after sorafenib monotherapy.…”

Molecular and Cellular Aspects of Cirrhosis and How an Adenosine Derivative Could Revert Fibrosis

“…Selected patients with localized disease may be treated with curative intents with resection, liver transplantation, or local therapy like radial frequency ablation, chemoembolization or radio-embolization. However, the majority of patients with HCC are not candidates for resection [104,105]. For patients suffering from advanced HCC, chemotherapy failed to demonstrate a survival advantage [106,107]; so far, sorafenib is the first and only target orientated agent approved as therapy of HCC [105], but it only extends survival of patients with advanced stage disease for 3 months, and this medication causes considerable adverse events and offers no symptom palliation [108].…”

Seven immune‐related genes prognostic power and correlation with tumor‐infiltrating immune cells in hepatocellular carcinoma

“…Liver cancer is one of the most important factors in tumor-related death, threatening thousands of lives worldwide. 1,2 The most common pathological type in liver cancer is hepatocellular carcinoma (HCC) which arises from chronic liver inflammation and liver fibrosis mostly. 3,4 Nowadays, surgical resection and liver transplantation are the most widely used treatments for HCC internationally.…”