ANXA1 mediates therapy resistance in CRC and RC by modulation of different pathways, such as PI3K/AKT/mTOR, PKC/JNK/P-gp, Wnt/β-catenin, and NF-κB, while promoting immune evasion, stem cell maintenance, and a significantly immunosuppressive TME by DC cell recruitment and macrophage polarization. The gene discussed is MAPK8; the disease is colorectal carcinoma.