Grant: CIHR Fellowship

Background: Epithelial ovarian cancer (EOC) remains the deadliest gynecological cancer as a result of asymptomatic presentation in >75% of women and < 29% 5-year survival rate when diagnosis occurs at late-stages. When EOC is treated at early-stages, 5-year survival rates exceed 95%, thus efforts to improve early-stage detection would drastically reduce the ~150,000 annual deaths. Unfortunately, current biomarkers (e.g. CA-125) lack the sensitivity and specificity to detect early-stage EOC; thus, identifying biomarkers with high sensitivity and specificity to early-stage EOC remains a priority. A collection of evidence suggests that extracellular vesicles (EVs) released from cancer cells can carry unique protein cargo and can be detected in blood plasma as a diagnostic marker for several diseases. Moreover, EVs are released by cancer cells into circulation and can travel to distant tissues to 'prime-the-soil' prior to metastasis. For these reasons, we hypothesize that EOC-derived EVs contain proteomic cargo that supports EOC metastasis and this cargo can be utilized as clinical biomarkers to detect early-stage EOC in blood plasma. Global Objective: My primary research aims will be to validate alternative clinical biomarkers capable of detecting early-stage EOC and to understand how extracellular vesicles released from EOC can 'prime' distant tissues for metastasis. Research Aims: In Aim 1, I will integrate quantitative proteomics using targeted mass spectrometry and machine learning classification algorithms to identify novel biomarkers on blood plasma EVs capable of identifying early-stage disease. The proposed research aims to develop diagnostic assays which will be advanced towards clinical trials. In Aim 2, I will understand how proteomic cargo within EOC EVs is regulated by translational control under hypoxia and how EOC EVs can activate distant cell populations prior to metastasis by integrating single-cell proteomic and transcriptomic technologies.