• Marcus Alexander Wörns and Peter Robert Galle.
• University Medicine of the Johannes Gutenberg-University Mainz, Department of Internal Medicine, Mainz, Germany. woerns@uni-mainz.de
• Expert Opin Investig Drugs. 2010 May 1; 19 (5): 615-29.

Importance Of The FieldThe multikinase inhibitor sorafenib was the first agent to demonstrate a survival benefit for patients with locally advanced or metastatic hepatocellular carcinoma (HCC). Although sorafenib represents a landmark in the treatment of HCC and proved molecularly targeted therapy to be effective in this disease, it represents just the first step towards an improvement in systemic therapy. Since then, novel inhibitors have been evaluated in early clinical trials, showing potential activity.Areas Covered In This ReviewThis article aims to review novel inhibitors emerging in the field of advanced HCC. An Internet-based search was performed to identify abstracts, clinical trials ( www.clinicaltrials.gov , last accessed 30 November 2009), and original research and review articles.What The Reader Will GainReaders will gain a comprehensive survey of current molecularly targeted therapy approaches in advanced HCC. In addition, challenges such as the design of clinical trials, the assessment of radiological response, the role of combination therapy, and future developments in molecularly targeted therapy are discussed.Take Home MessageSorafenib is the standard of care in patients with advanced HCC. However, promising novel inhibitors are under investigation. Combined molecularly targeted therapies according to an individual genomic and proteomic profiling will probably lead to more personalised medicine in advanced HCC.

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