De Novo Lipogenesis as a Therapeutic Vulnerability Linking Metabolism, Epigenetic Regulation, and Immunosuppression in DIPG

The recent clinical success of Modeyso (ONC201) in treating patients with DIPG highlights the therapeutic potential of targeting dysregulated metabolic pathways. Lipids serve as essential substrates for membrane biosynthesis, energy production, and signaling pathways. In contrast to normal cells, cancer cells frequently upregulate lipogenesis, thereby indicating this pathway as a potentially targetable metabolic vulnerability in DIPG. The overarching goal of this project is to define and therapeutically exploit lipogenesis as a metabolic dependency in DIPG by establishing a novel link between lipid metabolism, epigenetic regulation, and tumor-immune interactions, while also determining the mechanistic and therapeutic rationale for combination treatment with ONC201. These efforts are poised to advance our understanding of DIPG biology and accelerate the development of clinically actionable, metabolism-based therapies for children with DIPG.