This integrated approach would suppress the constitutively activated NF-κB signaling—a key driver of CRC treatment resistance—by eliminating TNFR1-mediated survival signals while reinstating VPS37A-dependent tumor suppression mechanisms, ultimately synergizing to induce programmed cell death and circumvent therapeutic evasion in VPS37A-deficient CRC. Here, NFKB1 is linked to colorectal carcinoma.