Vennetti Lab Offers a Flicker of Hope for Parents of Pediatric Cancer Patients
By Lynn McCain | July 1
One of the most heartbreaking things a parent can hear is “Your child has an aggressive, malignant brain tumor.” When that is followed up with the physician saying there is no effective cure, parents are left devastated. This is what motivates Dr. Sriram Venneti and his research laboratory to dedicate their all to finding a cure. Venneti focuses on Group 3 medulloblastomas, which are very aggressive pediatric brain tumors with no known cure.
Venneti’s team recently published their research where they sought to identify weaknesses in how these Group 3 medulloblastomas cancer cells function, so treatments could be developed. They found that patients who experienced worse outcomes have an increase in a protein called DLAT. DLAT is a key protein that helps metabolize glucose to generate energy in the mitochondria. Lowering DLAT disrupted key energy and protection processes in the cancer cells.
In addition, Group-3 medulloblastomas have characteristic cancer-driving genetic increases in a protein called c-MYC. They found that DLAT is activated by c-MYC. Additionally, another gene, IDH1, which helps regulate energy production, was also increased in Group-3 medulloblastomas. They observed that IDH1 controls both c-MYC and DLAT levels.
DLAT is involved in a unique type of cell death driven by copper, called cuproptosis, and Group-3 medulloblastoma cells were more sensitive to this process. Elesclomol is an FDA-approved drug that can reach the brain and trigger copper-dependent cell death. When Group-3 medulloblastoma tumors in pre-clinical animal models were treated with Elesclomol, the tumor cells died due to copper sensitivity. This work highlights a pathway that makes Group-3 medulloblastomas vulnerable to copper-dependent cell death. While additional studies are still needed, these findings offer a potential new approach to treating this deadly childhood brain tumor and a flicker of hope for future pediatric patients and their families.
Citation: Dang D*, Deogharkar A*, … Venneti S. Isocitrate Dehydrogenase 1 Primes Group-3 Medulloblastomas For Cuproptosis. Cancer Cell. volume 43, issue 7, 2025 July 15. (* indicates equal contribution) https://www.doi.org/10.1016/j.ccell.2025.04.013
ON THE COVER
ON THE COVER
ON THE COVER
ON THE COVER
ON THE COVER
ON THE COVER
ON THE COVER
ON THE COVER
ON THE COVER
ON THE COVER
