Chemoresistance is a significant obstacle to the successful treatment of ovarian cancer. Though standard chemotherapy regimens of cisplatin or carboplatin with paclitaxel are highly active and elicit substantial clinical response, resistance to these agents ultimately develops in nearly all patients. Molecular mechanisms of this drug resistance appear to involve multiple pathways modulated by many genes. The identification of genes that are expressed in correlation with response to chemotherapy will lead to improved understanding of these mechanisms and more effective treatment. We propose to use high-density cDNA expressed in ovarian cancer patients sensitive to chemotherapy relative to patients resistant to the same regimen. In this work, we will ascertain the relative frequencies of over and under- expression of genes known to be involved in chemoresistance. More importantly, this work will allow us to identify several dozen genes not previously associated with resistance to cisplatin and paclitaxel combination chemotherapy in ovarian cancer. The analysis of these novel genes will allow us to interpret their potential involvement in known resistance pathways. Though beyond the scope of this proposal, our findings will be useful in designing treatment strategies for overcoming resistance to chemotherapy and improving outcomes for patients suffering from ovarian cancer.
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