Evolving strategies for the treatment of hepatocellular carcinoma: from clinical-guided to molecularly-tailored therapeutic options

Hepatocellular carcinoma (hepatocellular carcinoma, HCC) is the commonest primary liver cancer (80-90%) and represents the leading cause of cancer-related death, after lung and stomach cancer. The process of neoplastic transformation proceeds through the accumulation of mutations in the genes governing cell proliferation and apoptosis. It is currently difficult to determine the natural history of patients with untreated early-stage HCC, since most with early-stage tumor patients undergoes curative therapy. Survival rates at 3 years is 65% in patients with Child-Pugh A, and single untreated lesion. This proportion increases to 70% at 5 years after radical treatment. In patients included in randomized controlled clinical trials with advanced disease, survival at 1 and 2 years is respectively 72% and 50%. Surgery is the only potentially curative treatment for HCC. In carefully selected patients, resection and transplantation in fact, allow a 5 years survival from 60% to 70%. Unfortunately most patients in Western countries present with an intermediate or advanced HCC at diagnosis with the consequent inability to use curative treatments. These patients are therefore candidates to palliative therapies that include arterial embolization and chemoembolization and systemic treatments including chemotherapy, immunotherapy and hormonal therapy. Only recently the molecular targeted drug, Sorafenib, has been introduced among the therapeutic options for these patients.