Cellular senescence and cancer treatment.
Cellular senescence, an irreversible cell-cycle arrest, reflects a safeguard program that limits the proliferative capacity of the cell exposed to endogenous or exogenous stress signals. A number of recent studies have clarified that an acutely inducible form of cellular senescence may act in response to oncogenic activation as a natural barrier to interrupt tumorigenesis at a premalignant level. Paralleling the increasing insights into premature senescence as a tumor suppressor mechanism, a growing line of evidence identifies cellular senescence as a critical effector program in response to DNA damaging chemotherapeutic agents. This review discusses molecular pathways to stress-induced senescence, the interference of a terminal arrest condition with clinical outcome, and the critical overlap between premature senescence and apoptosis as both tumor suppressive and drug-responsive cellular programs.
Schmitt
Clemens A
CA
Department of Internal Medicine/Hematology and Oncology, Charité-Universitätsmedizin Berlin (CVK), Augustenburger Platz 1, Berlin, Germany. clemens.schmitt@charite.de
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000187:drug effects / Q000502:physiology*; D004249:DNA Damage; D019008:Drug Resistance, Neoplasm; D006801:Humans; D009369:Neoplasms / Q000503:physiopathology* / Q000628:therapy*; D009857:Oncogenes / Q000502:physiology; D001616:beta-Galactosidase / Q000378:metabolism
D000970:Antineoplastic Agents; D001616:beta-Galactosidase