STAG1 is a component of cohesin, a ring-shaped protein complex involved in sister chromatid cohesion (SCC) that also plays important roles in the maintenance of chromatin structure, gene expression, and DNA repair. Cohesin consists of a core trimer and one of two mutually exclusive variant STAG subunits, STAG1 and STAG2. STAG1 is thought to primarily regulate telomeric cohesion, whereas STAG2 is primarily involved in centromeric cohesion (1,2). STAG2 mutations were detected in bladder cancer, Ewing sarcoma and acute myeloid leukemia. Targeting STAG1 represents a therapeutic opportunity in the treatment of STAG2-mutant cancers. Studies demonstrate that partial suppression of STAG1 triggers strong and selective anti-proliferative effects in STAG2-mutant cancer models (3).