Molecular Targeted Therapies in Hepatocellular Carcinoma: Past, Present and Future.
Hepatocellular carcinoma (HCC) is an aggressive tumor and the sixth most common form of cancer worldwide. Surgery is the gold-standard treatment for local disease and often complemented by radiofrequency ablation or transarterial chemoembolization. In advanced disease, therapy options are limited and relapse and metastasis are common. Systemic therapy with cytotoxic drugs such as doxorubicin and cisplatin achieves low objective response rates (typically <10%) and even sorafenib, an orally administered tyrosine kinase inhibitor considered a breakthrough when introduced, prolongs median survival by little more than a year. Sorafenib blocks platelet-derived growth factor, vascular endothelial growth factor, c-KIT and rapidly accelerated fibrosarcoma signaling, and belongs to a new class of targeted drugs. It has become standard treatment for advanced-stage HCC in recent years. To date, no other agent has been shown to be more effective than sorafenib in the clinical setting, which highlights the need for ongoing research to address this important clinical challenge. The current review focuses on recent advances in molecular targeted therapy for HCC. We explore the current status of evidence, identify areas of pressing experimental need, and provide an outline of promising future therapeutic options.
Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
Michael
M
Stotz
Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
Armin
A
Gerger
Institute of Pathology, Medical University of Graz, Graz, Austria.
Johannes
J
Haybaeck
Department of Internal Medicine I, Institute of Physiology and Pathophysiology, Paracelsus Medical University, Salzburg, Austria Laboratory for Tumor Biology and Experimental Therapies, Institute of Physiology and Pathophysiology, Paracelsus Medical University, Salzburg, Austria.
Tobias
T
Kiesslich
Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, U.S.A.
Marc D
MD
Bullock
Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, U.S.A. martin.pichler@medunigraz.at.
Martin
M
Pichler
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011379:Prognosis
D000970:Antineoplastic Agents; D009363:Neoplasm Proteins
Hepatocellular carcinoma; molecular-targeted therapy; review; sorafenib; tyrosine kinase inhibitor