Actionable heterogeneity of hepatocellular carcinoma therapy-induced senescence

Abstract

Die Dissertation ist gesperrt bis zum 31. Dezember 2025 !

Senescence is considered a critical cellular state in hepatocellular carcinoma (HCC) with relevance for both, progression as well as treatment. HCC is the most common form of liver cancer and the fourth-most leading cause of cancer-associated mortality worldwide. In recent years, several approaches have been conducted to utilize HCC therapy-induced senescence for treatment purposes. However, due to a lack of systematic studies, distinctions among TIS inducing treatments and potentially actionable targets arising from HCC TIS remain to be determined. In this study, we systematically compared the three TIS inducers etoposide, CX5461 and alisertib. Furthermore, we suggest that the distinct and selective characteristics of senescence in HCC could be utilized for various therapeutic strategies, including death receptor activation by agonistic antibodies or ligands, conventional monoclonal antibody immunotherapy, bi-and tri-specific antibody therapy, and cell therapy using CAR-NK or CAR-T cells.