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World J Hepatol. Mar 27, 2010; 2(3): 103-113
Published online Mar 27, 2010. doi: 10.4254/wjh.v2.i3.103
Medical treatment of unresectable hepatocellular carcinoma: Going beyond sorafenib
Camillo Porta, Chiara Paglino
Camillo Porta, Medical Oncology and Laboratory of Preclinical Oncology and Experimental Therapies, IRCCS San Matteo University Hospital Foundation, Pavia I-27100, Italy
Chiara Paglino, Medical Oncology, IRCCS San Matteo University Hospital Foundation, Pavia I-27100, Italy
Author contributions: Porta C and Paglino C equally contributed to this review.
Correspondence to: Camillo Porta, MD, Medical Oncology and Laboratory of Preclinical Oncology and Experimental Therapies, IRCCS San Matteo University Hospital Foundation, Piazzale C Golgi 19, Pavia I-27100, Italy. c.porta@smatteo.pv.it
Telephone: +39-382-501355 Fax: +39-382-502442
Received: August 17, 2009
Revised: January 14, 2010
Accepted: January 21, 2010
Published online: March 27, 2010
Abstract

Even though Sorafenib has radically changed the natural history of those hepatocellular carcinoma patients who are not amenable for curative treatments, further therapeutic improvements are badly needed. As it was for Sorafenib, our increasingly refined understanding of the complex mechanisms underlying HCC carcinogenesis are the starting point for the future development of such treatments. Presently, a number of molecularly targeted agents are in different stages of development for this once orphan cancer. Indeed, several pathways are presently being explored to identify potentially active drugs, including epidermal growth factor receptor, vascular endothelial growth factor/vascular endothelial growth factor receptors, mammalian target of rapamycin, phosphatidyl-inositol-3-kinase/Akt, insulin growth factor, Aurora kinase, Wnt/β-catenin, retinoic acid receptor and hepatocyte growth factor/C-Met. This review is aimed at addressing the results obtained so far with these newer drugs, also considering the challenges we shall face in the near future, including the issue of response evaluation and identification of predictive/prognostic biomarkers.

Keywords: Hepatocellular carcinoma; Molecularly targeted agents; Molecular pathways