We have shown that a specific subpopulation of cells, the ovarian cancer stem cells, may respond deferentially to treatment, being paradoxically stimulated by chemotherapeutics such as Doxorubicin and Cisplatin, while exhibiting an exquisite sensitivity to inhibition by the Müllerian Inhibiting Substance (MIS). The cancer stem cell is thought to be responsible for metastasis, chemoresistance and disease recurrence, underscoring the importance of targeting this subpopulation in future treatments for ovarian cancer. Recombinant MIS is currently in pre-clinical evaluation as a novel therapeutic for ovarian cancer for which our laboratory is currently pursuing a scale up of production. To assist in the design of a clinical trial we need to estimate the percentage of ovarian cancer patients who may respond to MIS, identify biomarkers that are predictive of response, and determine how we can recruit the immune system to enhance our treatment. To address these questions we will use primary cancer cells derived from patient ascites. This allows us to use a system that closely resembles advanced disease as it presents itself in patients while retaining the diversity contained in the patient population in a minimally invasive way. Preliminary evidence suggests that MIS both inhibits the ovarian cancer stem cells and stimulate the immune system by influencing the secretion of immune modulators by the these cells. Studying this response using patient-derived cancer cells will allow us to tailor MIS adjuvant therapy together with chemotherapeutic agents in future clinical trials in ovarian cancer. Furthermore, by focusing on the mechanism behind these properties of the cancer stem cell we hope to uncover additional therapeutic avenues for the treatment of ovarian cancer.