In a recent phase Ib clinical trial focusing on domatinostat (a dual inhibitor of LSD1/HDAC) in patients with advanced melanoma, the drug failed to enhance the efficacy of treatments targeting anti-PD-1 and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) while unexpected severe skin toxicity was observed.424 Furthermore, as current knowledge about these multitarget agents is still primarily derived from early-stage clinical trials, extensive investigations are necessary to validate their therapeutic value in a broader population. The gene discussed is CTLA4; the disease is melanoma.