PIK3CA and neoplasm: Interventions include combination therapy (e.g., PI3K inhibitors plus endocrine therapy for ESR1-mutant cancers) [67], next-generation inhibitors (e.g., tucatinib, which inhibits HER2 with improved BBB penetration), efflux pump inhibitors as chemotherapy adjuncts, and immunomodulatory drugs that target the reprogramming of the tumor immune microenvironment [77].