Chemotherapy for hepatocellular carcinoma: The present and the future

Abstract

Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver. Its relationship to chronic liver diseases, in particular cirrhosis, develops on a background of viral hepatitis, excessive alcohol intake or metabolic steatohepatitis, leads to a high incidence and prevalence of this neoplasia worldwide. Despite the spread of HCC, its treatment it’s still a hard challenge, due to high rate of late diagnosis and to lack of therapeutic options for advanced disease. In fact radical surgery and liver transplantation, the most radical therapeutic approaches, are indicated only in case of early diagnosis. Even local therapies, such as transarterial chemoembolization, find limited indications, leading to an important problem regarding treatment of advanced disease. In this situation, until terminal HCC occurs, systemic therapy is the only possible approach, with sorafenib as the only standard treatment available. Anyway, the efficacy of this drug is limited and many efforts are necessary to understand who could benefit more with this treatment. Therefore, other molecules for a targeted therapy were evaluated, but only regorafenib showed promising results. Beside molecular target therapy, also cytotoxic drugs, in particular oxaliplatin- and gemcitabine-based regimens, and immune-checkpoint inhibitors were tested with interesting results. The future of the treatment of this neoplasia is linked to our ability to understand its mechanisms of resistance and to find novel therapeutic targets, with the objective to purpose individualized approaches to patients affected by advanced HCC.

Keywords: Hepatocellular carcinoma, Systemic therapy, Chemotherapy, Molecular targeted therapy, Cytotoxic therapy, Immunotherapy, Perspectives

Core tip: The aim of this review is to make a point on chemotherapeutic options for treatment of hepatocellular carcinoma (HCC) at advanced stage, the most frequent stage of presentation of this neoplasia, still characterized by an important mortality rate. By now, sorafenib is the only standard treatment, but other options were recently studied and will be soon available for clinicians and patients affected by HCC. The review can be divided in four sections: The first one regards molecular target therapy and are described sorafenib, its open issues, but also other drugs with similar targets that have been evaluated for treatment of HCC. The second and the third parts regard cytotoxic drugs and immunotherapy, respectively, which were evaluated in recent years as possible alternatives or adjuvant to Sorafenib. In the last part of the review, future perspectives are described, in particular for what concerns resistance mechanism of the neoplasia, delivery methods or biological enhancers for drugs already in use, new drugs that will be probably evaluated and molecular targets that could soon become eligible for target therapy hopefully leading to the development of personalized therapy.