PRMT5/MAT2A synthetic lethality for MTAP-deleted mesothelioma
About half of mesotheliomas have lost a gene called MTAP. That loss creates a weakness that new PRMT5 inhibitors are designed to exploit.
CDKN2A/MTAP co-deletion occurs in ~40-50% of pleural mesotheliomas. MTAP loss raises MTA, which partially inhibits PRMT5; MTA-cooperative PRMT5 inhibitors (AMG 193, MRTX1719, BMS-986504) and MAT2A inhibitors show early responses in MTAP-deleted tumours including mesothelioma.
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