We integrate spatial genomics and single-cell data to map tumor location and molecular class to rational therapies, including CDK4/6, PI3K/AKT, YAP/TEAD, and epigenetic inhibitors, with emerging strategies such as synthetic-lethal combinations, CRISPR-guided target discovery, and degrader (PROTAC) approaches for high-grade and recurrent disease. The gene discussed is PIK3CA; the disease is neoplasm.