Functional and Genomic Comparison of Ovarian Cancer Cells in Ascites to Primary Tumor and Associated Cell-free DNA

At a Glance

This project aims to transform ovarian cancer care by repurposing tumor cell-containing abdominal fluid (ascites) samples from patients to identify markers of treatment resistance. The ability to easily assess risk of resistance in patients would potentially eliminate the use of ineffective therapy and serve as a signal for determining when second-line therapies should be explored.

The Challenge

Ovarian cancer, of which high-grade serous ovarian carcinoma (HGSC), accounts for five percent of all cancer deaths in females in the United States. Current standard of care for HGSC is platinum-based chemotherapy, but over half of patients are diagnosed with stage four disease and face a dismal, 32 percent, five-year survival rate. Around 80 percent of patients are considered sensitive to platinum-based chemotherapy, however patients display decreased response rates with each subsequent recurrence. Ovarian cancer patients often undergo periods of remission following initial surgery and platinum-based chemotherapy before ultimately recurring, frequently with resistance to the chemotherapy. Currently, the only way to determine if a patient is responsive to chemotherapy is to treat them and wait up to six months to determine response. Predicting platinum-refractory disease at the time of recurrence would eliminate an ineffective round of therapy for patients and signal to their physicians when second-line therapies should be explored.

Project Goals

The overarching goal of this project is to determine if the features of chemoresistance, previously identified in models, can be identified in samples from patients with ovarian cancer. Specifically, the researchers will examine blood plasma and tumor cell-containing abdominal fluid, called ascites. This goal will be addressed through two specific aims:

1. Genomic and functional comparison of subpopulations of tumor cells in ascites from ovarian cancer patients.
2. Comparison of genomic alterations and epigenetic markers in ascites and plasma cell-free DNA and primary tumor DNA.