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World J Gastroenterol. Jan 14, 2014; 20(2): 486-497
Published online Jan 14, 2014. doi: 10.3748/wjg.v20.i2.486
Molecular targeting agents associated with transarterial chemoembolization or radiofrequency ablation in hepatocarcinoma treatment
Girolamo Ranieri, Ilaria Marech, Vito Lorusso, Veronica Goffredo, Angelo Paradiso, Domenico Ribatti, Cosmo Damiano Gadaleta
Girolamo Ranieri, Ilaria Marech, Veronica Goffredo, Cosmo Damiano Gadaleta, Interventional Radiology Unit with Integrated Section of Translational Medical Oncology, National Cancer Research Centre, Cancer Institute “Giovanni Paolo II”, 70124 Bari, Italy
Vito Lorusso, Medical Oncology Unit, National Cancer Research Centre, Cancer Institute “Giovanni Paolo II”, 70124 Bari, Italy
Angelo Paradiso, Medical Oncology with Experimental Unit, National Cancer Research Centre, Cancer Institute “Giovanni Paolo II”, 70124 Bari, Italy
Domenico Ribatti, Department of Basic Medical Sciences, Neurosciences and Sensory Organs, Section of Human Anatomy and Histology, University of Bari, 70124 Bari, Italy
Author contributions: Ranieri G and Marech I contributed equally to the work; Ranieri G, Marech I and Gadaleta CD contributed to think up the manuscript and to perform the critical review of the literature; Lorusso V, Goffredo V, Paradiso A and Ribatti D contributed to literature research and data analysis. All authors wrote the manuscript.
Correspondence to: Girolamo Ranieri, MD, Interventional Radiology Unit with Integrated Section of Translational Medical Oncology, National Cancer Research Centre, Cancer Institute “Giovanni Paolo II”, Via Orazio Flacco 65, 70124 Bari, Italy. giroran@tiscalinet.it
Telephone: +39-80-5555561 Fax: +39-80-5555563
Received: August 11, 2013
Revised: September 26, 2013
Accepted: December 12, 2013
Published online: January 14, 2014
Abstract

Hepatocellular carcinoma (HCC) is the fifth most common cause of cancer in the world. According to Barcelona Clinic Liver Cancer modified criteria, patients with early stage disease are candidate to radiofrequency ablation (RFA), while patients with intermediate stage HCC are usually treated by transarterial chemoembolization (TACE). TACE and RFA induce a transient devascularisation effect followed by strong neo-angiogenic stimulus. In fact, after these procedures, it has been demonstrated an up-regulation of pro-angiogenic and growth factors such as vascular endothelial growth factor-A, which might contribute to accelerated progression in patients with incomplete response. Several studies have demonstrated that MAP-kinase and AKT pathways, in addition to neo-angiogenesis, have an important role in the development of HCC. In advanced HCC, anti-angiogenic therapy and tyrosine kinases inhibitors showed potential clinical benefit. Actually, a number of clinical studies are ongoing testing these agents in combination with TACE or RFA. In this paper, we have reviewed the most recent preclinical and clinical results of such trials.

Keywords: Hepatocellular carcinoma, Molecular targeting agents, Angiogenesis, Chemoembolization therapeutic, Radiofrequency treatment, Sorafenib

Core tip: The outcome of patients (with early or intermediate stage according to Barcelona Clinic Liver Cancer) treated with loco-regional approach alone [radiofrequency ablation (RFA) or transarterial chemoembolization (TACE)] is disappointing because the rebound of vascular endothelia growth factors induced by tissue hypoxia. On this basis there is a strong preclinical background to associate TACE or RFA with anti-angiogenic agents. We summarized the crucial role of angiogenesis and the pathways involved in hepatocellular cancer progression, underscoring the consequences of pro- and anti-angiogenic factors produced after loco-regional therapy. We explored preclinical and clinical results of trials combining molecular targeting agents plus TACE or RFA.