In December 2025, the Mike Slive Foundation awarded a research grant to Associate Professor Yiping He, PhD, to explore how an epigenetic regulator known as the COMPASS protein complex contributes to treatment resistance in prostate cancer. Working in collaboration with Johnston-West Endowed Chair of Pathology Jiaoti Huang, MD, PhD, the project will combine He’s expertise in cancer genetics with Huang’s deep knowledge of prostate cancer biology to advance strategies that may lead to more effective therapies for patients.
Today’s leading treatments for advanced prostate cancer work by blocking the androgen receptor, a protein that tumor cells rely on to grow. While these drugs can be effective at first, the cancer usually finds ways to adapt, stop responding, and recur. Researchers are working to understand how to prevent or delay this resistance.
As part of that effort, He’s team conducted a large screening study examining more than 19,000 proteins in prostate cancer cells. The aim was to find proteins that influence how well tumor cells respond to Enzalutamide (XTANDI), a commonly prescribed therapy that targets the androgen receptor. The study uncovered previously unrecognized proteins involved in drug sensitivity, including proteins in the COMPASS complexes. The COMPASS complex helps regulate how other proteins are produced in cells.
This complex is especially important for two reasons. First, genes encoding COMPASS proteins are mutated in about 20% of prostate cancers, and patients with these mutations tend to have poorer outcomes. Second, the research team’s analysis of large patient datasets shows that these genetic changes are linked to features that may make tumors more responsive to immunotherapy.
He’s study aims to answer two key questions:
- Can targeting COMPASS proteins make prostate cancer cells more responsive to Enzalutamide, and what exactly does this complex do inside these cells?
- How do mutations in the COMPASS proteins change the genetic makeup of prostate cancer, and how might these changes affect the tumor’s response to immunotherapy?
The study findings are expected to deepen the understanding of how prostate cancers become resistant to treatment and to guide the development of new strategies to overcome that resistance. They may also help identify patients who are most likely to benefit from existing immunotherapies.
The Mike Slive Foundation supports innovative research aimed at eliminating prostate cancer as a major public health threat. Advancing more effective treatments for patients with advanced disease remains a critical need.