title: [p53-regulating pathways as targets for personalized cancer therapy].
abstract: The tumor suppressor p53 acts as a transcription factor downstream of many different stress-induced signaling pathways. Two major groups of p53-controlled genes can be distinguished. Those that mediate the initiation and maintenance of cell cycle checkpoints, and those driving apoptosis. An important determinant of the cellular reaction to DNA damage is the degree of genotoxic stress. The type of cellular response, which ranges from cell cycle arrest to apoptosis depends to a large extend on the severity of the genotoxic lesion. It remains largely unclear which molecular mechanisms govern the cellular decision between p53-driven cell cycle arrest and apoptosis. From a therapeutic perspective, this cellular decision is of utmost importance, as p53-driven apoptosis is therapeutically desired, when treating a malignant disease with DNA-damaging chemotherapy. However, a p53-driven cell cycle arrest might promote chemotherapy resistance, as it allows the tumor cells time to repair genotoxic lesions prior to the next cell division. Here, we summarize recent advances in our understanding of the molecular mechanisms controlling the functional outcome of p53 signaling. We further provide an outlook on the potential development of pharmacological interventions targeting the p53-regulating machinery to promote p53-driven apoptosis, while repressing p53-dependent cell cycle checkpoints.
authors.affiliation: Klinik II für Innere Medizin, Uniklinik Köln.
authors.forename: K
authors.initials: K
authors.lastname: Höpker
authors.forename: H C
authors.initials: HC
authors.lastname: Reinhardt
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D016159:Tumor Suppressor Protein p53