Investigation of the Ubiquitin Ligase RNF31 as a Mediator of Immune Evasion in Advanced Prostate Cancer
Abstract
Scientific Objective, Rationale and Impact: Prostate cancer is the second leading cause of cancer-associated death in American men. While the 5-year survival rate for men with cancer localized to their prostate is nearly 100%, men with metastases, meaning the cancer cells have spread to other parts of the body, have a poor 5-year survival rate of 30%. Current therapies for these patients are non-curative and can only extend survival by a few months. Therefore, there is a critical need to improve treatment options for patients with lethal prostate cancer. Immunotherapy is a novel treatment strategy that enhances and directs the body’s own immune system to target cancer cells while sparing normal healthy cells. While immunotherapy have been drastically successful and potentially curative in many cancers, it has met with limited success in prostate cancer. One reason is that prostate cancer cells have evolved to lower the surface levels of a key molecule called major histocompatibility complex (MHC), which prevents T-cells, a major cancer-killing player of our immune system, from recognizing them. Fortunately, natural killer (NK) cells, another cancer-killing immune cell, can function independently of MHC expression and show promise in prostate cancer. We hypothesize that there are druggable genes and pathways that can make prostate cancer more susceptible to NK-associated killing. Our preliminary data showed that reducing the levels of a molecule called RNF31 in cancer cells will enhance killing by NK cells. The goal of this proposal is to understand how this happens and evaluate novel treatment options to improve immunotherapy. Answers to these questions will help identify new treatments options that can significantly extend the lives of patients with advanced prostate cancer. Career Goals in Prostate Cancer Research: My keen interest in biology and personal motivation from the passing of a family member due to cancer have led me toward a career in prostate cancer research, which I have initiated by obtaining my Ph.D. degree studying prostate cancer biology. During my studies, I became aware of critical areas of research that can help overcome barriers to prostate cancer treatment and transform the lives of those affected, and I aspired to pursue my career in the area of immunotherapy. It is my career goal to become an independent prostate cancer scientist and lead my own research group in conducting translational research to help improve the lives of patients. With this goal in mind, I joined Dr. Felix Feng’s laboratory to apply my existing skillsets to this new research area and further train myself towards an independent scientist. This project will allow me to advance my understanding of the immune landscape of prostate cancer and barriers to immunotherapy and gain new skillsets necessary for my career goals. I will also benefit tremendously from guidance and expertise of my co-mentors, Drs. Feng and Lanier, who are internationally recognized leaders in the field of prostate cancer and immunology, respectively. My co-mentors and I have devised a multifaceted training plan that will not only focused on my scientific development, but also essential non-scientific skillsets, to ensure the success of this proposed project and advancement towards my ultimate career goals. I am dedicated to this proposed project, and I firmly believe that, if selected, this award will be an invaluable asset in helping me achieve my career goals.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210107
Entities
People
- Tianyi Liu
Organizations
- United States Army
- University of California, San Francisco