title: The dual role of mutant p53 protein in chemosensitivity of human cancers.
abstract: Mutational loss of p53 tumor suppressor functions has been observed in a wide range of neoplasms and was associated with either enhanced or decreased chemosensitivity of affected tumors. The dual role of wild-type p53 as a DNA repair initiator and a trigger for apoptosis raises the possibility that appropriately designed chemotherapy could be selectively applied against p53-defective tumor cells. The cytotoxic effects of DNA-crosslinking chemotherapeutica such as cisplatin could be enhanced by mutated p53 which is no longer able to repair drug-induced DNA damage. In contrast, DNA synthesis blockers such as fluorouracil can induce apoptosis through p53-dependent mechanisms. Thus, loss of p53 functions results in decreased sensitivity to this type of drugs. Clinical studies will reveal the role of abberant p53 in the efficacy of chemotherapy for individual patients.
authors.affiliation: Department of Gynecology, University Hospital Basel, Switzerland.
authors.forename: H
authors.initials: H
authors.lastname: Mueller
authors.forename: U
authors.initials: U
authors.lastname: Eppenberger
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D004249:DNA Damage; D004260:DNA Repair; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D009154:Mutation; D009336:Necrosis; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*
chemical_list: D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53