Abstract
Hepatocellular carcinoma (HCC) remains a highly complex disease resistant to commonly used chemotherapy and radiotherapy. As the fifth most common cancer worldwide with the third highest mortality rate and very poorly understood molecular pathways driving hepatocarcinogenesis, new treatment strategies are urgently needed for this devastating disease. The multi kinase inhibitor Sorafenib was the first molecular targeted drug in HCC that led to significant survival benefit in patients with advanced tumors. It is the first drug to be considered standard of care for advanced HCC and supports the importance of molecular therapies in the treatment of this cancer. Analysis of genetic and epigenetic alterations as well as different molecular pathways involved in the development of HCC help to identify potential new druggable targets. A variety of novel compounds are already under preclinical or clinical investigation, and accumulating evidence suggests that combination therapy targeting different pathways will potentiate anti-tumoral effects and will become the future therapeutic approach. In addition, the establishment of a robust molecular classification will pave the way for a more personalized treatment scheme in HCC. In this article a review of the current knowledge of the molecular pathogenesis of HCC and an overview of molecular targeted therapies in the management of HCC are provided.
Highlights
Hepatocellular carcinoma (HCC) is the fifth leading cancer in the world and more than 80% of cases occur in Asia
The FDA (US Food and Drug Administration) and EMEA (European Medicine Agency) approval of sorafenib followed shortly after, and a consensus of several HCC expert panels recommended that sorafenib should be the standard of care for the treatment of advanced HCC, as well as the control-arm that novel compounds for the treatment of HCC need to be tested against in future clinical trials [18]
The success of sorafenib is proof of the principle that molecular therapy plays an important role in the treatment of advanced HCC
Summary
Hepatocellular carcinoma (HCC) is the fifth leading cancer in the world and more than 80% of cases occur in Asia. Even though Hepatitis B and C is the most common cause of HCC, a variety of risk factors have been identified. These include hereditary hemochromatosis, and cirrhosis of almost any cause. Most of HCC cases develop from a cirrhotic liver, with an annual incidence of 2-6% for hepatitis B virus carriers and 3-5% for hepatitis C virus-infected patients. 7.5 Lakhs of new cases of HCC per year occurs globally which makes HCC as the 5th common cause of cancers effecting humans [1]. The mortality in HCC is very high; about 7 Lakhs death due to HCC occur annually and has been estimated to be the third common cause of death due to cancers effecting humans [1]. The cancer registries in India probably do not provide accurate estimates of HCC prevalence due to its predominant urban locations and the source of information on cancers are from cytology, oncology sites, and municipal registers of death
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