Ovarian cancer treated with PARP inhibitors (PARPi), like olaparib, initially responds well in many patients whose tumors carry BRCA mutations or other DNA-repair deficiencies, but resistance develops in a large fraction of patients over time, often detected only after a tumor has visibly progressed on imaging or through an invasive repeat biopsy. How resistant cells signal or adapt at a molecular level, and whether this can be detected earlier and non-invasively, is not fully understood. One way cells communicate their internal state is by releasing extracellular vesicles (EVs), tiny membrane-bound particles that carry proteins reflecting the condition of the cell that produced them. For my project, I will compare EVs released by PARPi-sensitive ovarian cancer cell lines to EVs released by their olaparib-resistant counterparts, focusing on candidate resistance-associated proteins such as SMYD3 and SAMHD1. Using nano-flow cytometry (CytoFLEX Nano), I will profile these EVs for marker expression and compare results across sensitive cell lines, resistant cell lines, and patient-derived organoid models. The goal is to determine whether resistant cells shed a distinct EV signature that could serve as an early, blood-based indicator of PARPi resistance. With my project I hope to reduce reliance on invasive biopsies or frequent imaging, and potentially improve equitable access to timely treatment changes for patients with limited access to specialized monitoring.
Northeastern University
