Hepatocellular Carcinoma: A Difficult Cancer to Treat.

Hepatocellular carcinoma (HCC) is a very peculiar cancer because it presents several molecular alterations linked to the activation of survival and antiapoptotic signal pathways that are protein in form and not easily targetable by even the newest targeted therapies. In addition, it is almost always a consequence of liver cirrhosis, a serious disease condition in which several drugs are often not tolerated. This is why the study of HCC was such a challenge for Professor Natale D'Alessandro, to whom this work is dedicated, during the latter years of his career. The aim of this review is to summarize studies on different molecules involved in the development, progression, and chemoresistance of HCC, topics on which we have focused our research over the last decade. In particular, we have analyzed the role of inflammatory mediators, such as the cyclooxygenase (COX) enzymes, nuclear factor κB (NF-κB), interleukin 6 (IL-6), as well as other important factors, such as Yin Yang 1 (YY1), in HCC. Moreover, we have reviewed some more recent literature on research aimed at identifying druggable targets in HCC as well as candidate agents for its prevention and treatment.