Taken together, ANXA1 contributes to CRC chemoradioresistance by multiple interconnected mechanisms, such as the modulation of hypoxia-driven responses, activation of survival and drug efflux pathways, inhibition of autophagy, and enhancement of oncogenic signaling, such as PI3K/Akt/mTOR, NF-κB, and Wnt/β-catenin, providing a promising therapeutic target. The gene discussed is AKT1; the disease is colorectal carcinoma.