Relationship between alterations in the p53 gene and chemosensitivity of ovarian cancers
It is thought that the cytotoxic effect of chemotherapy drugs is largely due to their ability to initiate programmed cell death (apoptosis). Although the molecular pathways involved in regulation of apoptosis have not been completely elucidated, it has been shown that the p53 tumor suppressor gene plays a significant role in this process. Mutations in the p53 gene are a frequent event in ovarian cancers and it has been postulated that loss of functional p53 might confer resistance to chemotherapy drugs such as cisplatin, alkylating agents and paclitaxel. The data in the literature do not consistently support this hypothesis, however. Although some experimental studies have suggested mutant p53 is associated with a resistant phenotype, other studies have clearly demonstrated that chemosensitivity is not solely determined by the status of the p53 gene. The current body of evidence suggests that regulation of chemotherapy induced apoptosis involves a complex series of molecular events. As the intricacies of these pathways are unraveled, hopefully these insights will prove useful in predicting chemoresponsiveness of individual ovarian cancers.
Berchuck, A; Maxwell, GL; Marks, JR
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