Clinical Oncolytic Virus-Based Therapy For Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC), also called malignant hepatoma, is the most common type of livercancer. HCC is the third leading cause of cancer deaths worldwide, with over 500,000 peopleaffected. It carries a poor prognosis, because the advanced disease is resistant to both radiotherapyand conventional cytotoxic drugs which have limited therapeutic index and lots of treatmentrelatedside effects. Therefore, new therapeutic strategies are needed to selectively destroy thetumor cells and leave the normal cells undamaged. Viral oncotherapy is a promising treatment thatoffers unique chance for tumor targeting. Oncolytic viruses (OVs) are designed to replicate in andlyse cancer cells. The premise of OVs lies in their preferential genomic replication, proteinexpression and productive infection of malignant cells. Different OVs have been tested inpreclinical models of HCC, with reasonable evidence of anti-tumor efficacy. Efforts to influence theperformance of these agents have concentrated on engineering OV cellular specificity, immuneevasion, enhancing anti-tumor potency and improving delivery. The lead agent in HCC clinicaltrials, JX-594, a recombinant Wyeth strain vaccinia virus, that was genetically modified to inactivethe endogenous thymidine kinase gene and to express human GM-CSF and LacZ genes, hasdemonstrated evidence for important benefit and earned orphan drug status. Thus, JX-594 seems tobe transcending the barrier between novel laboratory science and credible clinical therapy. Fewother OVs have entered clinical testing, which is an obstacle that must be destroyed if importantprogress is to be made in this field.This article indicated that viral oncotherapy can be effective ontreating hepatocellular carcinoma.