Berkley Gryder, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund

What is the problem? Fusion-positive rhabdomyosarcoma is a rare and deadly childhood cancer of muscle tissue. It is caused by a rearranged fusion gene (PAX3-FOXO1) that acts like an “on switch” stuck in the “on” position. Only 39% of children with this cancer are alive five years after diagnosis. Today there is no targeted drug that attacks the root cause of the disease.What is “enhancer addiction”? The rearranged gene does not work alone. It hijacks two helper proteins, called CBP and p300, which chemically tag regions of DNA to keep cancer genes turned on. These tags build up at the cancer’s “enhancer” switches, and the cancer cells become addicted to them. Take away the tags and the cancer loses power.What will this project do? Our lab invented a new medicine called IHK-44 that blocks CBP and p300 from turning on enhancer (gene “on” switches). Over five years, we will (1) show exactly how the medicine stops enhancer addiction, (2) develop a tumor test that predicts which children will benefit most, and (3) make IHK-44 safer and more potent by tuning its chemistry. Then we will test it in mouse models of this cancer. Why does this matter? If IHK-44 works, it will become the first precision medicine designed specifically for fusion-positive rhabdomyosarcoma. This project is the critical step that moves a new drug from the laboratory toward clinical trials, giving children with this cancer a real chance at a longer, healthier life.