Using Peptide-Based Tools to Overcome Drug Resistance in Colorectal Cancer

This is a narrative review article that synthesizes recent research on peptide-mediated therapies against drug-resistant colorectal cancer. The authors surveyed preclinical studies and clinical evaluations of peptide-drug conjugates, cell-penetrating peptides, pro-apoptotic peptides, oncolytic peptides, immunotherapeutic peptides, and peptide-nanocarrier systems.

Colorectal cancer is a leading cause of cancer death, and drug resistance severely limits treatment effectiveness. Peptide-based approaches offer a versatile toolkit for attacking resistance through multiple mechanisms simultaneously. If validated clinically, these strategies could restore treatment sensitivity in patients whose cancers have stopped responding to conventional therapies.

Peptide therapeutics are increasingly recognized for their versatility in oncology. While antibody-drug conjugates have gained clinical traction, peptide-drug conjugates offer advantages in terms of smaller size, better tissue penetration, and lower immunogenicity. This review positions peptide scaffolds as a complementary approach to existing cancer therapies, particularly for the growing problem of multidrug resistance that affects many colorectal cancer patients.

The evidence reviewed is primarily preclinical — most peptide-based strategies discussed have not been validated in human clinical trials. The proposed MRP Framework is a conceptual tool that needs clinical validation. Peptide stability, bioavailability, and manufacturing scalability remain practical challenges. The review does not quantify efficacy across studies with specific outcome data.