Taken together, these findings suggest that extracellular PrP<sup>C</sup> supports RAS-AKT signaling, proliferation, and tumor-associated angiogenesis in KRAS-mutant colorectal cancer, and that PrP<sup>C</sup> neutralization additively enhances 5-fluorouracil activity in KRAS-mutant models. The gene discussed is AKT1; the disease is neoplasm.