基礎医学特論　TOKURON

基礎医学特論　TOKURON

日時：令和7年6月27日（金）18:00〜19:50Date and Time: June 27, 2025 (Fri)6:00 pm – 7:50 pm言語：英語Language: English場所：基礎研究棟会議室2（生協横）Venue: Meeting Room No.2, Basic Medical Research Building (1st Floor)講演者 Speaker: Balveen Kaur, PhDTitle: oncolytic vital therapy for cancerAbstract:Identification of IDH mutations has uncovered the crucial roleplayed by metabolism in gliomagenesis. Oncolytic herpes virus (oHSV) therapyinitiates direct tumor debulking by tumor lysis and activates antitumorimmunity, however, little is known about the role of glioma metabolism indetermining oHSV efficacy. Here we identify that oHSV rewires central carbonmetabolism increasing glucose utilization towards oxidative phosphorylation andshuttling glutamine towards reductive carboxylation in IDH wildtype (wt)glioma. The switch in metabolism results in increased lipid synthesis and cellularROS. PKC induces ACSL4 in oHSV treated cells leading to lipid peroxidation andferroptosis. Ferroptosis is critical to launch an antitumor immune responsewhich is important for viral efficacy. Mutant IDH (IDHR132H) gliomas areincapable of reductive carboxylation and hence ferroptosis. Pharmacologicalblockade of IDHR132H induced induces ferroptosis and antitumor immunity. Thisstudy provides a rationale to use an IDHR132H inhibitor to treat high gradeIDH-mutant glioma patients undergoing oHSV treatment.