Editorial [Hot Topic:Resent and Future Therapies for the Hepatocellular Carcinoma (Executive Editor: G. Giannelli)]

Hepatocellular carcinoma (HCC) is becoming a major health problem worldwide, both because of the constantly rising number of patients and of the poor prognosis of this disease. Therapies adopted so far mainly fight the cancer by removing the tumor or the whole liver whenever possible by transplantation, or by destroying it either by alcoholization, radiofrequency ablation (RFA) or transarterial chemoembolization (TACE). The clinical outcome is often unsatisfactory and cancer recurrence or metastatic spread are common events that severely affect prognosis and survival. No therapies are yet available to cure HCC, and this is rather surprising since for all other cancer forms, newly introduced pharmacological therapies have greatly improved survival. The concomitant liver cirrhosis where HCC commonly develops hampers the use of chemotherapeutics, which pose an increased risk due to the already reduced liver functionality. As in other cancers, the idea is emerging that biological therapies may offer new hope for patients with HCC. In vitro results support this view and a better definition of the proper target of these drugs is gaining increasing importance, in order to improve their efficacy. This issue deals with the important issue of therapies for HCC, including all the novelties introduced in the traditional but still important therapies, although particular attention will be devoted to the new strategies for biological therapies. The first part of the issue discusses the therapies currently in use. However, this is not just an update on the current state of the art, although this would already be a relevant issue, but rather focuses on the future of these approaches, that will surely be milestones in the up-coming years, while new biological therapies acting as sharper bullets are being developed. In this regard, Lee Gordon and co-authors from the University of Vanderbilt, USA, have discussed the role of liver transplantation as a possible therapy for concomitant treatment of the HCC and underlying liver cirrhosis [1]. Michel Beaugrand and co-authors from the Hopital Jean Verdier, France, have focused mainly on the use of locoregional therapies, that are currently widely used, and discuss the future applications of these techniques thanks to improved technologies [2]. The second part of the issue is dedicated to defining the biological and molecular bases regulating the biological properties of HCC, essential for the future development of target-oriented therapies. In this regard, Stefania Tommasi and co-authors from the National Cancer Institute of Bari, Italy, have discussed the role of genes involved in proliferation, metastatization and apoptosis as potential targets for future therapies [3]. Salvatore Antonaci and co-authors from the University of Bari, Italy, have reviewed the emerging role of the tissue microenvironment as a biological regulator of HCC behavior, in order to explain the role of different components potentially targeted by currently available biological therapies [4]. However, the next step will be to address how to develop a therapeutic strategy integrating the advances in more basic scientific fields in biomedical research. This is discussed in depth by Dipankers Chattopadyhay and co-authors from Newcastle University, UK [5]. There is no question that translational research is becoming highly relevant for the medical sciences, and this paper and the whole issue aim to set an example in this sense. Finally, Gianluigi Giannelli and co-authors from the University of Bari, Italy, have reviewed the literature on the use of a promising class of drugs, tyrosine-kinase inhibitors targeted against the tissue microenvironment, as therapy for HCC [6]. Marco Breinig and co-authors from the University of Heidelberg, Germany, have discussed another interesting and intriguing class of molecules, COX-2 inhibitors, with an antitumor ability. This is an old class of molecules that has recently been reconsidered for use as therapies directed against the microenvironment components, that could provide new insight in the field of anti-cancer therapies [7].