Drs. Yu, Corces, Peng, and Zhao contribute to prostate cancer study that offers hope for new treatments
JULY 2025
A first-of-its kind study led by Emory researchers has uncovered how prostate cancer transforms into the aggressive neuroendocrine form of the disease. The study also identified a promising new treatment strategy in the process. The findings, published in Nature Genetics, offer critical insights into why some prostate cancers become resistant to therapy and how that shift could be blocked.
Emory Human Genetics faculty Jindan Yu (senior author), Victor Corces, Peng Jin, and Jonathan Zhao worked with other investigators from multiple disciplines to create a 3D map of how prostate cancer cells rewire over time to become a new threat. The map showed how the DNA folds and loops inside the cell nucleus to activate genes driving the transformation.
The researchers discovered that two proteins — FOXA2 and NKX2-1 — play a central role in this process. FOXA2 acts as a pioneer, opening up regions of DNA that are normally inaccessible. This allows NKX2-1, a gene typically found in brain and lung cells, to activate a new set of instructions that reprogram the cancer cells into NEPC. Together, they reshape the cell's identity and drive its transition to a deadlier form.
The study also revealed that enzymes called CBP and p300 are essential for this transformation as they evolve to turn on a new set of oncogenes (targets). Importantly, the researchers showed that CBP/p300-inhibiting drugs, such as CCS1477, currently in clinical trials, are able to target the moving targets and stop NEPC tumor growth in lab and animal models.
This research has major implications for patients, families, and the future of prostate cancer treatment, and could aid in the development of new therapies that could dramatically improve outcomes.