Tucker Gosnell Center for Gastrointestinal Cancers, Massachusetts General Hospital Cancer
Center, Harvard Medical School, Boston, Massachusetts.

　It is well appreciated that hepatocellular carcinoma (HCC) represents one of the most challenging
malignancies of worldwide importance. In fact, HCC is the fifth most common cancer and the third
most common cause of cancer-related death globally. The incidence rates for HCC in the U.S. and
Western Europe have been rising. Unresectable or metastatic HCC carries a poor prognosis, and
systemic therapy with cytotoxic agents provides marginal benefit. Because of the poor track record of
systemic therapy in HCC, there has been a sense of nihilism for this disease in the oncology
community for decades. However, with the arrival of newly developed, molecularly targeted agents and
the success of some of these agents in other traditionally challenging cancers, such as renal cell
carcinoma, there has been renewed interest in developing novel systemic therapy in HCC. At the recent
Annual Meeting of the American Society of Clinical Oncology, results of a phase 3, randomized,
placebo-controlled trial were presented in which sorafenib demonstrated improved survival in patients
with advanced HCC. This landmark study represents the first agent that has demonstrated an improved
overall survival benefit in this disease and sets the new standard for first-line treatment of advanced
HCC. For this review, the author concisely summarized the current status of molecularly targeted
agents that are under clinical development in advanced HCC. Cancer 2008. (c) 2007 American Cancer
Society.