1 Department of Medical Sciences and Chronobiology Laboratory, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo (FG), Italy.
2 Fondazione Policlinico Universitario A Gemelli-IRCCS- Catholic University of the Sacred Heart, 00168 Rome, Italy.
3 Bioinformatics Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo (FG), Italy.
4 International Clinical Research Center (FNUSA-ICRC), St. Anne's University Hospital, 65691 Brno, Czech Republic.
The biological clock controls at the molecular level several aspects of mammalian physiology, by regulating daily oscillations of crucial biological processes such as nutrient metabolism in the liver. Disruption of the circadian clock circuitry has recently been identified as an independent risk factor for cancer and classified as a potential group 2A carcinogen to humans. Hepatocellular carcinoma (HCC) is the prevailing histological type of primary liver cancer, one of the most important causes of cancer-related death worldwide. HCC onset and progression is related to B and C viral hepatitis, alcoholic and especially non-alcoholic fatty liver disease(NAFLD)-related milieu of fibrosis, cirrhosis, and chronic inflammation. In this review, we recapitulate the state-of-the-art knowledge on the interplay between the biological clock and the oncogenic pathways and mechanisms involved in hepatocarcinogenesis. Finally, we propose how a deeper understanding of circadian clock circuitry-cancer pathways' crosstalk is promising for developing new strategies for HCC prevention and management.