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Abstract Cellular senescence has gained great interest in the recent years following the demonestration that it also occurs in vivo. Cellular senescence is the phenomenon by which normal diploid cells lose the ability to divide normally after about 50 cell divisions. Some cells become senescent after fewer replication cycles as a result of DNA damaging agents. This cell cycle arrest is irreversible and occurs at G1phase of the cycle. Telomere shortening , oncogenes and reactive oxygen species (ROS) are the most leading causes of this senescence response mainly through activation of the gatekeeper tumor supressor genes p53 and pRb. This provides a strong barrier against malignant transformation by preventing unlimited cell proliferation. Senescent cells can be identified by the presence of cytological markers of senescence, which include mainly senescence associated β-galactosidase (SA-βgal), senescence associated heterochromatic foci (SAHF), senescence associated DNA-damage foci (SDFs) and p16. These cells are good citizins, bad neighbours via alteration of their local microenvironment. Liver cirrhosis represents the senescent stage of hepatocellular carcinoma (HCC) with increased expression of senescence markers. The appearance of proliferating malignant cells from this senescence stage requires the bypass of senescence barrier through inactivation of senescence-mediator genes, as well as reactivation of telomerase reverse transcriptase (TERT). Although senescence represents a new weapon for cancer therapy, the appearance of senescence associated secretory phenotype (SASP) limits the role of senescence induction as a possible cancer therapy. Conclusion • Understanding the tumor suppressor mechanisms of cellular senescence will increase our knowledge about the potential role of senescence as a potent cancer therapy. • The development of senescence based therapeutics provides a promising tool in cancer treatment. • Also, knowledge of the cellular signaling pathways implicated in HCC and the role of senescence induction in HCC regression can open new therapeutic opportunities. Although there are still many challenges to overcome, it is quite clear that senescence research is promising and may be the backbone of many of the most cutting-edge medical therapies of tomorrow. |