Animal Models: A Useful Tool to Unveil Metabolic Changes in Hepatocellular Carcinoma

SIMPLE SUMMARY: Hepatocellular carcinoma (HCC) represents an important health problem. At the moment, systemic therapies offered only modest clinical benefits. Thus, HCC represents a cancer extremely difficult to treat, and therapeutic breakthroughs are urgently needed. Metabolic reprogramming of neoplastic cells has been recognized as one of the core hallmarks of cancer. Experimental animal models represent an important tool that allows to investigate metabolic changes underlying HCC development and progression. In the present review, we characterize available rodent models of hepatocarcinogenesis. Moreover, we discuss the possibility that pharmacological targeting of Warburg metabolism may represent an additional tool to improve already available therapeutic approaches for HCC. ABSTRACT: Hepatocellular carcinoma (HCC) is one the most frequent and lethal human cancers. At present, no effective treatment for advanced HCC exist; therefore, the overall prognosis for HCC patients remains dismal. In recent years, a better knowledge of the signaling pathways involved in the regulation of HCC development and progression, has led to the identification of novel potential targets for therapeutic strategies. However, the obtained benefits from current therapeutic options are disappointing. Altered cancer metabolism has become a topic of renewed interest in the last decades, and it has been included among the core hallmarks of cancer. In the light of growing evidence for metabolic reprogramming in cancer, a wide number of experimental animal models have been exploited to study metabolic changes characterizing HCC development and progression and to further expand our knowledge of this tumor. In the present review, we discuss several rodent models of hepatocarcinogenesis, that contributed to elucidate the metabolic profile of HCC and the implications of these changes in modulating the aggressiveness of neoplastic cells. We also highlight the apparently contrasting results stemming from different animal models. Finally, we analyze whether these observations could be exploited to improve current therapeutic strategies for HCC.