Despite advances in radical surgery and chemotherapy delivery, ovarian cancer is the most lethal gynecologic malignancy.\nStandard therapy includes treatment with platinum-based combination chemotherapies yet there is no biomarker model to\npredict their responses to these agents. We here have developed and independently tested our multi-gene molecular\npredictors for forecasting patients� responses to individual drugs on a cohort of 55 ovarian cancer patients. To\nindependently validate these molecular predictors, we performed microarray profiling on FFPE tumor samples of 55 ovarian\ncancer patients (UVA-55) treated with platinum-based adjuvant chemotherapy. Genome-wide chemosensitivity biomarkers\nwere initially discovered from the in vitro drug activities and genomic expression data for carboplatin and paclitaxel,\nrespectively. Multivariate predictors were trained with the cell line data and then evaluated with a historical patient cohort.\nFor the UVA-55 cohort, the carboplatin, taxol, and combination predictors significantly stratified responder patients and\nnon-responder patients (p = 0.019, 0.04, 0.014) with sensitivity = 91%, 96%, 93 and NPV = 57%, 67%, 67% in pathologic\nclinical response. The combination predictor also demonstrated a significant survival difference between predicted\nresponders and non-responders with a median survival of 55.4 months vs. 32.1 months. Thus, COXEN single- and\ncombination-drug predictors successfully stratified platinum resistance and taxane response in an independent cohort of\novarian cancer patients based on their FFPE tumor samples.
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