Because of limits on specificity and purity to allow for indepth protein profiling, a standardized method for exosome isolation has yet to be established. In this study, we describe a novel, in-house microfluidic-based device to isolate exosomes from culture media and patient samples. This technology overcomes contamination issues because sample separation is based on the expression of highly specific surface markers CD63 and EpCAM. Mass spectrometry revealed over 25 exosome proteins that are differentially expressed in high-grade serous ovarian cancer (HGSOC) cell lines compared with normal cells-ovarian surface epithelia cells and fallopian tube secretory epithelial cells (FTSEC). Top exosome proteins were identified on the basis of their fold change and statistical significance between groups. Ingenuity pathway analysis identified STAT3 and HGF as top regulator proteins. We further validated exosome proteins of interest (pSTAT3, HGF, and IL6) in HGSOC samples of origin-based cell lines (OVCAR-8, FTSEC) and in early-stage HGSOC patient serum exosome samples using LC/MS-MS and proximity extension assay. Our microfluidic device will allow us to make new discoveries for exosome-based biomarkers for the early detection of HGSOC and will contribute to the development of new targeted therapies based on signaling pathways that are unique to HGSOC, both of which could improve the outcome for women with HGSOC. Significance: A unique platform utilizing a microfluidic device enables the discovery of new exosome-based biomarkers in ovarian cancer.

PARP inhibitors have shown significant promise in the treatment of ovarian cancer. Olaparib is a PARP inhibitor that has been approved for maintenance for BRCA-mutated ovarian cancer in the recurrent and front-line setting as well as for treatment of BRCA-mutated ovarian cancer in patients who have received multiple prior lines of chemotherapy. In this review, we focus on the use of olaparib in the maintenance setting including the evidence to date, ongoing research, and future directions.

No abstract

No abstract