Funded by the Kay Yow Cancer Fund
Ovarian cancer (OC) is the deadliest gynecological cancer. The standard treatment approach for epithelial OC is the combination of a platinum compound, mainly carboplatin and taxane. Although most women initially respond well to treatment, the vast majority experience disease recurrence within 2 years, resulting in a fatal relapse due to chemoresistance. Thus, the development of carboplatin resistance is a major barrier in OC treatment. To date, no effective approaches have been developed to overcome carboplatin resistance. We hypothesize that high expressions of some key proteins lead to carboplatin resistance in OC. Recently, we have developed the innovative validation-based insertional mutagenesis (VBIM) technique for novel gene discovery. In this proposal, our overall objective is to use the VBIM technique, in combination with bioinformatics and other advanced approaches, to identify key proteins that lead to carboplatin resistance in OC cells. Human OC cell lines and OC tumor tissues will be used as our research tools. Overall, our unique and comprehensive approach could yield a set of completely novel carboplatin resistance proteins which might not be discovered using traditional methods. The important findings generated from this work will guide physicians to design more rational and precise therapies with greater effectiveness in a specific OC patient. Moreover, this work could open future opportunities for reversal of carboplatin resistance by developing small molecule inhibitors. Therefore, this work would have a fundamentally transformative effect on OC chemotherapy.