Targeting MAT2A-S-adenosylmethionine (SAM) Axis Attenuates DNA Damage Response and Cancer Stemness to Increase Platinum Sensitivity in Ovarian Cancer

This preprint proposes a MAT2A indication that the one MAT2A failure on file did not test. BG-89894 was developed for MTAP-deleted solid tumours and was closed in a portfolio decision rather than on an efficacy readout (bg-89894-mat2a-mtap-portfolio-shutdown), so the graph carries no evidence that MAT2A inhibition fails to produce clinical benefit. The synthetic lethal rationale differs as well. The MTAP-deletion strategy depends on methylthioadenosine accumulation sensitising cells to MAT2A loss, while the mechanism here is platinum sensitisation through SAM-dependent methylation and DNA repair in cells that are not selected for MTAP status. A programme following this work would be entering with a different patient selection hypothesis and should not be discounted by the earlier shutdown, though it inherits the same open question about whether MAT2A inhibitors achieve durable SAM suppression at tolerated exposures in patients.