[Hepatocellular carcinoma: novel therapeutic approaches].

Therapeutic options for patients with hepatocellular carcinoma (HCC) are still limited. Only patients with small HCC are considered for curative treatment options such as resection, liver transplantation or local ablation. Systemic treatment of advanced HCC is still impaired by the high level of resistance to chemotherapy and irradiation. In addition, most patients with HCC are highly susceptible to toxic side effects due to their impaired liver function. Novel treatment options are based on the increasing understanding of molecular mechanisms involved in tumorigenesis, tumor progression and metastasis. Such "targeted therapies" aim at growth factors and their receptors, intracellular signal transduction and cell cycle control. Anti-angiogenesis targets the tumor vasculature. Gene therapeutic strategies are based on the transfer of therapeutic genes in target tissues to express highly active proteins such as suicide genes or cytokines. Tumor cell death by cell lysis is the mechanism of oncolytic viruses, which are able to selectively replicate in tumor cells. This mechanism may be augmented by the addition of therapeutic genes expressed by recombinant oncolytic viruses. The induction of a potent immune response to tumor antigens by vaccination strategies or by adoptive transfer of activated immune cells aim at the specific destruction of tumor cells by effector T-cells targeted to tumor antigens.