CPTAC: Proteogenomic Studies of Ovarian Tumor Responses to Agents Targeting the DNA Damage Response

There is a critical unmet need for predictors of chemo-refractory High-grade serous ovarian cancer (HGSOC). Despite over 3 decades of research on platinum responses in cancer, no predictive biomarker has been translated into clinical use. Predictors of refractory disease could spare these patients the unnecessary toxicity of a platinum-based regimen and provide a means to triage these patients to clinical trials to identify effective therapies for refractory disease. This study has approached the development of a predictor in a novel way enabling detection of a multi-analyte panel biomarker capable of detecting a subset of refractory HGSOCs with high specificity and implicating potential treatment vulnerabilities for refractory disease. We reported the first proteogenomic analysis of platinum refractoriness in HGSOC and made the novel dataset available as a resource to the community, including a ProTrack portal: http://ptrc.cptac-data-view.org/. Detailed proteogenomic profiles were generated for this study from a retrospective cohort of 242 treatment-naive HGSOCs with enriched representation of "exceptional non-responders" (i.e., patients with chemo-refractory disease). Whole genome sequence (WGS) and RNA seq FASTQ files are available through dbGaP. Proteomic data are available through the NCI Proteomic Data Commons (PDC): https://pdc.cancer.gov/pdc/. ]]>
Treatment-naive tissue specimens from Stage III or IV HGSOCs that underwent primary debulking followed by platinum/taxane adjuvant therapy were selected for the study and categorized with respect to response to adjuvant chemotherapy. Refractory tumors were defined as follows. After primary debulking, for R0 disease (no residual/microscopic disease after primary resection), radiographically detectable disease must have been present at the end of 6 cycles of initial platinum/taxane therapy; for R1 disease (radiographically detectable residual disease is present after primary resection), residual disease must either progress or stay stable (radiographically) after 6 cycles of initial platinum/taxane therapy.Sensitive tumors were defined by R1 or R2 disease that received primary resection followed by platinum/taxane adjuvant therapy and had a progression-free survival of at least 2 years (no R0 disease). ]]>