APC and colorectal cancer: Of patients assigned to NCI-MATCH subprotocols, 54.0% of patients with actionable alterations also had co-occurring mutations in tumor-suppressor genes that have been implicated in therapeutic resistance in settings such as PI3Kα inhibitors in PIK3CA-mutant cancers and BRAF inhibitors in BRAF-mutant melanoma and colorectal cancer (TP53, 45.0%; KRAS, 13.8%; or APC, 12.5%), but these did not preclude treatment assignment.17,18 Activating mutations in genes that also contribute to oncogenesis—ERBB2, CCND1, and NF1—were found in 13.2% of patients.