Investigation of the Androgen Receptor as a Regulator of MHC Class I Expression and Immune Evasion in Advanced Prostate Cancer
Abstract
Scientific Objective and Rationale: Prostate cancer is the second leading cause of cancer-associated deaths in men. While the 5-year survival rate for patients with cancer localized to their prostate is nearly 100%, men with metastatic disease that has spread to other parts of their body is invariably fatal. Current therapies for these patients are only able to extend survival by a few months; therefore, there is an urgent need to improve treatments for patients with advanced prostate cancer. Immunotherapy is a treatment option that stimulates a patient’s immune system to specifically eliminate cancer cells without harming healthy cells, leading to less toxic side effects and improved quality of life for cancer patients. Unfortunately, this treatment strategy has had limited success in prostate cancer. It is known that prostate cancer cells have lower levels of surface molecules, called the major histocompatibility complex (MHC), which the immune system uses to recognize cancer cells. We hypothesize that increasing the expression of these MHC surface molecules will help prostate cancer patients respond better to immunotherapy. Preliminary data from our laboratory has shown that the androgen receptor (AR) is involved in the downregulation of MHC in prostate cancer cells. The goal of this proposal is to further elucidate the role of AR in regulating MHC expression and evaluate its effect on immunotherapy. Answers to these questions will help identify new combination treatments of preexisting androgen-targeted treatments and immunotherapy to significantly extend the lives of patients with advanced prostate cancer with less toxic side effects. Career goals: Initially, it was a family member’s diagnosis that led me toward a career in prostate cancer research. Since joining Dr. Felix Feng’s laboratory in 2018, I have been able to apply my background in pharmacology, as well as expand my skill set into cancer immunotherapy research in order to improve the treatment options for patients with metastatic prostate cancer. Becoming a part of the Prostate Cancer Research Program at the University of California at San Francisco and collaborating with other prostate cancer experts across the country has solidified my desire to become a permanent member of this community. I am constantly in awe of the collaborative nature and resource-sharing that is used to make significant advances in the prostate cancer field. This project will give me the opportunity to advance my knowledge in prostate cancer using new technologies, mouse modeling, and sequencing analysis of tumor samples from treated patients. My mentors and I have devised a training plan consisting of prostate cancer and immunology seminars, monthly meetings, and workshops to acquire the expertise necessary to successfully complete this project. I will also tremendously benefit from Dr. Feng’s experience in translational prostate cancer research and Dr. Charles Drake’s expertise in immunotherapy, as well as their mentorship during weekly meetings to share my data and access my progress. My ultimate goal is to lead my own research group focused on understanding mechanisms of drug resistance in patients with metastatic castration-resistant prostate cancer and developing novel therapy treatments for subsets of prostate cancer patients. I am dedicated to this career plan and know that, if selected, this award will be an invaluable asset in helping me distinguish myself as an independent researcher.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110046
Entities
People
- Lisa Chesner
Organizations
- United States Army
- University of California, San Francisco