bioRxiv· Taglang, C., Udutha, S., Phoenix, T. N., Lathia, J. D., de Groot, J., Viswanath, P. ·· 13 hours agoPickScore60
GLP1R agonists and vorasidenib converge on peroxynitrite-mediated cytotoxicity in mutant IDH glioma
In brief
GLP1R agonists and vorasidenib produce synergistic cytotoxicity through the peroxynitrite pathway in patient-derived and mouse models of mutant IDH glioma. Mechanistically, GLP1R agonists induce nitric oxide production via cAMP-PKA signaling, while vorasidenib relieves D-2HG-mediated inhibition of pyruvate dehydrogenase and increases mitochondrial superoxide; the two converge to form peroxynitrite that damages lipids and DNA and triggers apoptosis. The combination induces tumor regression and significantly prolongs survival in mice bearing intracranial mIDH tumors.
Why it matters
The synergistic killing provides a mechanistic basis for clinical evaluation of this combination in mIDH glioma.
Source: bioRxiv