These observations are important because suggest differential therapeutic approaches for these patients: second-generation AR-directed therapies for mCRPC with AR pathway alterations; PI3K inhibitors for a part of patients with cancer-related gene alterations (i.e., PIK3CB-specific inhibitors for patients with alterations of this gene, MEK inhibitors for patients with RAF kinase fusions, and PARP inhibitors for patients with biallelic inactivation of BRCA2, BRCA1, or ATM). The gene discussed is PIK3CB; the disease is cancer.