Researchers from the University of Tokyo, University of Ryukyus, and Daiichi Sankyo Co. used single-cell technologies, including Chromium Single Cell ATAC and Gene Expression assays, to uncover the mechanisms of action and resistance of valemetostat, a dual inhibitor targeting EZH1 and EZH2, in treating adult T-cell leukemia/lymphoma (ATL). They found that valemetostat reduces H3K27me3 levels, leading to chromatin relaxation and reactivation of tumor suppressor genes, which improves patient outcomes. Additionally, the treatment increases expression at previously repressed gene loci, countering the epigenetic repression observed in cancer cells. By exploiting Chromium Single Cell ATAC, these findings open a new realm of therapy development, offering promising directions for more effective and durable cancer treatments.