This paradigm shift has demonstratedpromising efficacy in preclinical and clinical studies, especiallyin cancer therapy. Notably, recent PhaseIII clinical trial results demonstrated that vepdegestrant (also knownas ARV-471), a PROTAC targeting the estrogen receptor (ER), prolongedprogression-free survival in patients with ER-positive, HER2-negativeadvanced breast cancer, although the benefit was limited to the subgroupharboring ESR1 mutations and was not observed in the overall patientpopulation. The gene discussed is ESR1; the disease is cancer.