Application of this model to over 11,000 tumor genomes across ~30 cancer types revealed that chemotherapeutic exposure can induce treatment-associated selection in genes including PIK3CA, APC, MAP2K4, SMAD4, STK11, and MAP3K1, each of which contributes to critical signaling networks governing tumor survival, EMT, and immune evasion. Here, APC is linked to neoplasm.