ScholarWorks@중앙대학교

초록

Purpose Pancreatic cancer exhibits high mortality due to its aggressive nature, late-stage detection, and dense desmoplastic stromal barriers that exclude larger biologics like monoclonal antibodies. This review explores the utility of peptides (~1–2 kDa) as molecular tools, given their unique capacity to bypass high interstitial fluid pressure and provide rapid tissue penetration, high specificity, and adaptability for diagnostic and therapeutic applications. Methods We evaluate contemporary peptide discovery platforms, including phage display, rational design, and “one-bead-one-compound” (OBOC) combinatorial libraries used to identify high-affinity ligands for tumor-associated markers. Additionally, the review investigates the emerging field of immunopeptidomics to identify cryptic (noncanonical) peptides derived from traditionally “noncoding” genomic regions. Results Peptide-based strategies yield significant diagnostic innovations, such as the GB-6 peptide targeting gastrin-releasing peptide receptors (GRPR) and pH-responsive probes that exploit the acidic tumor microenvironment for high-contrast imaging. Therapeutically, immunopeptidomics addresses the scarcity of classical neoantigens in pancreatic cancer—which typically has a low-to-intermediate mutational burden—by uncovering shared, cancer-restricted antigens. These noncanonical targets show strong translational potential for personalized TCR-redirected T cell therapies, demonstrating robust cytotoxicity against patient-derived organoids. Conclusion Despite hurdles related to in vivo metabolic stability and pharmacokinetics, peptide-based strategies offer a highly adaptable approach to overcoming the physical and immunological barriers of pancreatic cancer. The future of precision oncology in this domain relies on integrating multifunctional peptide-drug conjugates with noncanonical antigen targeting to achieve earlier detection and more effective, durable treatments.

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