Grant: Project Grant - Priority Announcement: Early Detection/Cancer Prevention

Neuroendocrine prostate cancer (NEPC) is one of the most aggressive forms of prostate cancer. Unlike other types, it does not rely on androgen receptor (AR) signals to grow. This makes it resistant to current hormone-based treatments and drugs that target AR. Right now, the only treatment option for NEPC is chemotherapy, which is highly toxic and offers only limited survival benefits. There is an urgent need for better, more effective treatments. One unique feature of NEPC is a "closed" arrangement of structures inside the cell's nucleus. This suggests that certain factors controlling these structures may play an important role in how NEPC develops. Using our state-of-the-art laboratory model of NEPC, we discovered that a gene called CHD7, which has never before been linked to NEPC, acts as a key regulator of these nuclear changes. Our early studies confirmed that change of CHD7 is relevant to NEPC in patients and plays an important role in the disease. Notably, when we reduced CHD7's activity, NEPC cells grew more slowly and became more sensitive to existing chemotherapy, pointing to a promising new treatment approach. In this project, we aim to confirm CHD7's role in NEPC, figure out exactly how it helps cancer cells grow, and test whether targeting CHD7 (and related factors) together with chemotherapy could create a more effective and less toxic treatment for patients. This work will deepen our understanding of NEPC and open the door to new targeted treatment strategies. If successful, it could lead to better therapies and improved outcomes for people facing this highly aggressive form of prostate cancer.