Dr Ellis Highlights Novel Approach That May Boost Prostate Cancer Immunotherapies

Hello, my name is Leigh Ellis, and I am currently the scientific director of the Center for Urological Research Excellence at Cedars-Sinai Cancer and Associate Professor of Medicine in the Division of Medical Oncology, Department of Medicine and Biomedical Sciences at Cedars-Sinai Medical Center.

Today, I would like to share some of latest findings recently published in Nature Cancer, and what our findings could potentially mean for prostate cancer patients.

The introduction of check-point blockade immunotherapy (CPI) has significantly changed the therapy landscape for many cancers, but unfortunately overall response to CPI in prostate cancer patients has been less than impressive. Therefore, it is critically important to understand how prostate cancer mediate resistance to CPI.

Epigenetics is the term used to describe how a cell regulates gene expression – switching genes on and off to maintain homeostasis. Our work in the lab focuses on epigenetic mechanisms driven by a protein known as enhancer of zeste homolog-2 (EZH2). EZH2 has been previously demonstrated to be overexpressed in prostate cancer.

Our recent findings, published in Nature Cancer, show that EZH2 is involved in suppressing certain genes critical to allow the prostate cancer cell to be recognized by the patient’s own immune system and destroyed. This data showed that our prostate cancer model systems were resistant to CPI. By inhibiting the function of EZH2, important immune genes within the cancer cell were switched back on (or re-expressed). These genes, called interferon-response genes that have multiple functions including, making the cancer cell visible to the immune system and also attracting more anti-tumor immune cells into the tumor microenvironment. Importantly, EZH2 inhibition reversed resistance to CPI.

With these exciting results, a Phase 2 clinical trial will now proceed in prostate cancer patients to provide evidence that EZH2 inhibition can indeed reprogram the prostate cancer and its tumor microenvironment to generate sensitivity to CPI. Together, this will provide an important breakthrough that will allow prostate cancer patients to experience the full benefit of having their own immune system brought back into the fight against their disease.