KDM1A and Ewing sarcoma: In Ewing sarcoma, acquired resistance to the reversible LSD1 inhibitor SP-2509 occurs without the emergence of LSD1 mutations and is instead associated with transcriptional reprogramming, down-regulation of CoREST1, up-regulation of drug efflux transporters, and increased sensitivity to HDAC inhibitors—suggesting a shift in epigenetic dependency (241).