Restoring VPS37A function through oncolytic adenoviruses, CRISPR/Cas9 ribonucleoproteins for precise gene editing, or lipid nanoparticles encapsulating optimized VPS37A mRNA or mimicking its degradative activity on TNFR1 using PROTACs for ubiquitin-proteasome disposal or LYTACs for lysosomal trafficking may represent promising therapeutic avenues for CRC, particularly in advanced-stage tumors where metabolic stress and NF-κB hyperactivation converge to drive lethality. This evidence concerns the gene TNFRSF1A and colorectal carcinoma.