title: DNA damage is able to induce senescence in tumor cells in vitro and in vivo.
abstract: Often the use of cytotoxic drugs in cancer therapy results in stable disease rather than regression of the tumor, and this is typically seen as a failure of treatment. We now show that DNA damage is able to induce senescence in tumor cells expressing wild-type p53. We also show that cytotoxics are capable of inducing senescence in tumor tissue in vivo. Our results suggest that p53 and p21 play a central role in the onset of senescence, whereas p16(INK4a) function may be involved in maintaining senescence. Thus, like apoptosis, senescence appears to be a p53-induced cellular response to DNA damage and an important factor in determining treatment outcome.
authors.affiliation: Department of Medical Oncology, St. Bartholomew's Hospital, London.
authors.forename: Robert H
authors.initials: RH
authors.lastname: te Poele
authors.forename: Andrei L
authors.initials: AL
authors.lastname: Okorokov
authors.forename: Lesley
authors.initials: L
authors.lastname: Jardine
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Cummings
authors.forename: Simon P
authors.initials: SP
authors.lastname: Joel
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis; D004249:DNA Damage / Q000502:physiology*; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D000077146:Irinotecan; D020360:Neoadjuvant Therapy; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000502:physiology; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C493956:CDKN1A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53; D005047:Etoposide; D000077146:Irinotecan; D001616:beta-Galactosidase; D002166:Camptothecin