Are Peptides Linked to Cancer?
Peptides have a dual relationship with cancer: certain endogenous peptides serve as diagnostic biomarkers for neuroendocrine tumors, while therapeutic peptides are increasingly used as targeted anticancer agents with lower toxicity than conventional chemotherapy.
Peptides as Cancer Biomarkers
Neuroendocrine Tumor Detection
Chromogranin A (CgA) is the primary general marker for neuroendocrine tumors (NETs), found in high concentrations regardless of hormone-related clinical features, and is elevated in approximately 75% of carcinoid tumors 1, 2.
5-hydroxyindoleacetic acid (5-HIAA), a serotonin breakdown product, serves as a specific marker for serotonin-producing NETs, with approximately 90% specificity for carcinoid syndrome and 70% sensitivity for midgut carcinoids 1, 2.
Pancreatic polypeptide is secreted in high concentrations from 50-80% of pancreatic NETs and over 30% of all gut NETs, making it a useful additional marker when CgA or chromogranin B are within reference range 1, 3.
Clinical Application of Peptide Markers
For midgut carcinoids, measure both CgA and 24-hour urinary 5-HIAA as 5-HIAA sensitivity reaches 70% for this location 2, 3.
For foregut carcinoids, prioritize CgA over 5-HIAA as 5-HIAA is only occasionally elevated in these tumors 2, 3.
For hindgut carcinoids, use CgA exclusively as 5-HIAA is not raised in these tumors 2, 3.
Up to 20% of patients with gastric NETs may develop another synchronous cancer, typically affecting the gastrointestinal tract, indicating peptide markers can signal increased cancer risk 1.
Peptides as Anticancer Therapeutics
Mechanism of Action
Therapeutic peptides can directly target cancer cells without affecting normal cells, offering an alternative to conventional chemotherapy with lower toxicity to normal tissues 4, 5, 6.
Anticancer peptides induce cell death through multiple mechanisms including membrane disruption and necrosis, apoptosis induction, tumor angiogenesis inhibition, immune regulation, disruption of cell signaling pathways, and interference with DNA repair pathways 7.
Peptides can act as carriers of cytotoxic agents and radioisotopes by specifically targeting cancer cells, as exemplified by fam-trastuzumab deruxtecan-nxki, which links HER2-targeting antibody to a topoisomerase I inhibitor 1, 4.
Clinical Evidence
Fam-trastuzumab deruxtecan-nxki achieved a 55% objective response rate in patients with metastatic NSCLC and ERBB2 mutations, with median overall survival of 17.8 months 1.
Peptide-based hormonal therapy has been extensively studied for breast and prostate cancers with substantial clinical data supporting efficacy 4.
Combination therapy using peptides with conventional treatments is emerging as an important strategy to achieve synergistic effects, as single-method approaches may not be efficient enough 4.
Peptides and Cancer Risk Assessment
Neoantigen Prediction
Neoantigens are newly formed peptides created from somatic mutations that are capable of inducing tumor-specific T cell recognition and are being leveraged for personalized cancer immunotherapies 1.
High clonal neoantigen burden is associated with an inflamed tumor microenvironment and improved response to immune checkpoint therapy in lung cancer patients 1.
Patients whose tumors exhibited a large proportion of subclonal mutations (>50%) were less likely to benefit from immune checkpoint therapy, suggesting clonal neoantigens elicit more effective immune responses 1.
Safety Considerations
- In the ORIGIN study of 12,537 patients followed for median 6.2 years, insulin glargine (a peptide hormone) showed no increased cancer risk with similar incidence of any cancer event compared to standard care (hazard ratio 0.99,95% CI 0.88-1.11) 8.
Critical Pitfalls to Avoid
Relying solely on 5-HIAA for NET diagnosis without considering other biomarkers may miss 30% of midgut carcinoids and the majority of foregut and hindgut carcinoids that don't produce significant serotonin 2.
Dietary restrictions must be enforced 48 hours before and during 5-HIAA collection: avoid avocados, bananas, pineapples, plums, walnuts, tomatoes, coffee, and alcohol to prevent false-positive results 2, 3.
Proton pump inhibitors, renal/hepatic insufficiency, and atrophic gastritis can falsely elevate CgA levels independent of neuroendocrine tumor presence 2.
Therapeutic peptides face challenges with protease degradation and absorption once administered, requiring modification strategies to improve bioavailability and anticancer effects 5, 7.