Cellular Senescence in Hepatocellular Carcinoma: The Passenger or the Driver?

With the high morbidity and mortality, hepatocellular carcinoma (HCC) represents a major yet growing burden for our global community. The relapse-prone nature and drug resistance of HCC are regarded as the consequence of varying intracellular processes and extracellular interplay, which actively participate in tumor microenvironment remodeling. Amongst them, cellular senescence is regarded as a fail-safe program, leading to double-sword effects of both cell growth inhibition and tissue repair promotion. Particularly, cellular senescence serves a pivotal role in the progression of chronic inflammatory liver diseases, ultimately leading to carcinogenesis. Given the current challenges in improving the clinical management and outcome of HCC, senescence may exert striking potential in affecting anti-cancer strategies. In recent years, an increasing number of studies have emerged to investigate senescence-associated hepatocarcinogenesis and its derived therapies. In this review, we intend to provide an up-to-date understanding of liver cell senescence and its impacts on treatment modalities of HCC.