Understanding and overcoming resistance to PARP inhibitors in ovarian cancer patients
Michelle Wang with Dr. Cesar Martin Castro (MGH)
Extracellular vesicles, or EVs, are membrane particles that are continuously secreted from cells. Such particles are reported to be carriers of proteins, nucleic acids, and lipids from their parent cells, making them prime targets for use in liquid biopsies. Previous studies have shown that EVs are promising circulating biomarkers for cancer diagnosis, but our understanding of their roles in predicting treatment responses is currently limited. Specifically in gynecologic cancers, PARP inhibitors are used as treatment against PARP protein such that DNA damage repair is hindered, ultimately leading the cell to die. However, many patients suffer from eventual resistance to PARP inhibitor treatment, and thus it would be clinically impactful if we could identify when it occurs using liquid biopsies. EVs are particularly useful in researching this mechanism as their characterization can help detect relevant protagonists in the pathway of PARP inhibitors or measure protein levels to determine how well the drug is working. Over the course of my co-op, I will be working to characterize cancer cells and their resistance to PARP inhibitors using EVs from unpurified human clinical samples including ascites and blood.