title: New molecularly targeted therapies against advanced hepatocellular carcinoma: From molecular pathogenesis to clinical trials and future directions.
abstract: Hepatocellular carcinoma (HCC) can be lethal due to its aggressive course and lack of effective systemic therapies for advanced disease. Sorafenib is the only systemic therapy that has demonstrated an overall survival benefit in patients with advanced HCC, and new agents for treatment of advanced HCC are needed. The multiple pathways involved in HCC oncogenesis, proliferation and survival provide many opportunities for the development of molecularly targeted therapies. Molecular targets of interest have expanded from angiogenesis to cancer cell-directed oncogenic signaling pathways for treatment of advanced HCC. Agents targeting vascular endothelial growth factor receptor, epidermal growth factor receptor, fibroblast growth factor receptor, platelet-derived growth factor receptor, c-mesenchymal-epithelial transition factor-1 and mammalian target of rapamycin signaling have been actively explored. This article focuses on the evaluation of molecular agents targeting pathogenic HCC and provides a review of recently completed phase III drug studies (e.g. involving sorafenib, sunitinib, brivanib, linifanib, erlotinib, everolimus, ramucirumab or orantinib) and ongoing drug studies (e.g. involving lenvatinib, regorafenib, tivantinib or cabozantinib) of molecularly targeted agents in advanced HCC, including a brief description of the biologic rationale behind these agents.
authors.affiliation: Department of Gastroenterology and Hepatology, Hokkaido University, Sapporo.|Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Chuma
authors.affiliation: Department of Gastroenterology and Hepatology, Hokkaido University, Sapporo.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Terashita
authors.affiliation: Department of Gastroenterology and Hepatology, Hokkaido University, Sapporo.
authors.forename: Naoya
authors.initials: N
authors.lastname: Sakamoto
keywords: clinical trials; hepatocellular carcinoma; molecularly targeted therapy; novel agents; sorafenib