Research And Grants

Sumoylation as a Novel Therapeutic Target in DIPG

SUMOylation is a post-translational protein modification (PTM) involved in the control of gene regulation, DNA damage repair, immune responses, and tumor growth.  During the process, SUMO proteins are attached to target proteins by SUMOylation enzymes. Because of its importance in cancer, SUMOylation inhibitors are being developed as therapeutic agents. Subasumstat (TAK-981) is a first in-class SUMOylation inhibitor that disrupts SUMOylation. TAK-981 is now in multiple oncology clinical trials in patients with advanced cancers. Nothing is known about the importance of SUMOylation in DIPG. We discovered that SUMOylation genes are elevated in DIPG compared to normal brain and most other pediatric brain tumors. When tested in several DIPG cell lines, the SUMOylation inhibitor TAK-981 killed 70-90% DIPG cells in the Petri dish. In this grant we will test the efficacy of the drug in our mouse models of DIPG in combination with radiation. In addition to DIPG, SUMOylation genes are also elevated in two other pediatric brain tumors with poor outcomes - group 3 medulloblastoma and Atypical Teratoid Rhabdoid Tumor (ATRT). If the results of our studies in DIPG hold true in these two brain tumors, our research may have a broader impact in finding treatments for children with brain tumors.