The evaluation of amphiregulin as a novel immunomodulatory high grade serous ovarian cancer therapy

Project summary

High grade serous ovarian cancer is the most lethal of all gynecologic cancers. While patients typically respond well to chemotherapy, often their disease returns, and they become unresponsive to treatment. Therefore, in order to improve patient prognosis, there is an urgent need to better understand factors that influence chemotherapy response and resistance.

In recent years, efforts have focused on the development of targeted therapies that function to activate the patient’s immune system to fight tumor cells, called immunotherapies; however ovarian cancer patients have been largely unresponsive to these current treatments. It has been theorized that this lack of response is due to the complex and unique nature of the ovarian tumor microenvironment, a network composed of multiple cell types that surround and influence the tumor.

Our group’s previous work has identified that the gene amphiregulin is highly overexpressed in patient tumors following chemotherapy exposure and is significantly upregulated in patients that have chemoresistant disease. This investigation will examine how amphiregulin affects the ovarian tumor immune microenvironment as well as determine the efficacy of targeting this factor alone and with chemotherapy and immunotherapy. Ultimately, results from this research will, for the first time, generate an unprecedented understanding of the immune-mediated mechanistic and therapeutic effects of amphiregulin in the context of ovarian cancer.