Up to 52% of CUP have clinically meaningful tumor-agnostic alterations, including mutations in PIK3CA, ERBB2, BRAF, and NTRK, and molecular signatures such as microsatellite instability–high and tumor mutational burden–high.75 Actionable mutation-driven treatment is currently being evaluated by the CUPISCO trial. This evidence concerns the gene ERBB2 and neoplasm.