NIH ProtIG Seminar by Stefani Thomas: Development of proteogenomic ovarian cancer biomarkers: diagnostic of disease stage and predictive of therapeutic response

Currently, no clinical test is approved by the US FDA to screen the general population for ovarian cancer – the most lethal gynecologic malignancy in women. Additionally, to improve the selection of patients with ovarian cancer who are most likely to benefit from targeted therapy, there is a critical need to adopt analytical approaches beyond conventional genomic scar assays. Ovarian cancer patients experience a broad spectrum of clinical benefit in response to targeted therapy based on their tumor mutational profile. Mass spectrometry (MS)-based proteomic and proteogenomic approaches can address these gaps in clinical care. Traditional antibody-based immunoassays to measure protein biomarkers have significant limitations such as low-multiplexing, low inter-laboratory reproducibility, and lack of antibody specificity. Targeted MS assays can overcome these limitations. Our efforts to develop and conduct analytical validation of a multiplexed, targeted MS parallel reaction monitoring (PRM) assay for the relative quantification of a panel of putative ovarian cancer protein biomarkers in serum (n=69 women) will be discussed. Our insights into the proteogenomic determinants of response to poly(ADP)-ribose polymerase inhibitors (PARPi) and histone deacetylase inhibitors (HDACi) in the context of targeted therapy for BRCA-mutated high-grade serous ovarian cancer will also be shared.Air date: 1/11/2024 1:00:00 PM
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