Clinical and experimental contributions to the study of phenotypic changes in chemotherapy-treated hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the 5th most common malignant tumor and the second leading cause of cancer-related death. Thanks to a better knowledge of the complex molecular mechanisms related to hepatocarcinogenesis, some targeted therapies are currently used in patients with unresectable tumoral disease and good liver function. The aim of this PhD was mainly to study the toxicity and antitumor efficacy of sorafenib and salirasib treatment in a model of chemically induced HCC in rats. The potential risk of tumoral phenotypic changes secondary to these therapies, with the development of a hepatocholangiocarcinoma has been further investigated. This phenomenon, already described in humans especially after hepatic transarterial chemoembolization or radiofrequency, is extremely important since it could modify the management of HCC-patients awaiting for liver transplantation.