Marine Bioactive Peptides for Colorectal Cancer Therapy: Mechanisms, Therapeutic Potential, and Translational Challenges.

Colorectal cancer (CRC) is one of the most prevalent gastrointestinal malignancies worldwide and remains a major cause of cancer-related mortality. Although current treatment strategies, including surgery, chemotherapy, radiotherapy, and targeted therapies, have improved patient outcomes, their effectiveness is frequently limited by multidrug resistance, severe adverse effects, tumour recurrence, and restricted patient applicability. Consequently, there is an urgent need to develop novel therapeutic agents with improved efficacy and reduced toxicity. Marine bioactive peptides have emerged as promising candidates for CRC therapy because of their remarkable structural diversity, unique evolutionary adaptations, and broad spectrum of biological activities. Numerous marine-derived peptides exhibit potent anti-CRC effects by inducing apoptosis, regulating cell-cycle progression, suppressing invasion and metastasis, inhibiting angiogenesis, and modulating the tumour microenvironment while generally demonstrating low toxicity toward normal cells. Despite these advantages, the clinical translation of marine peptides remains constrained by several challenges, including poor stability, rapid enzymatic degradation, limited bioavailability, difficulties in large-scale production, insufficient target characterization, and a lack of long-term safety evaluation. Recent advances in peptide engineering and pharmaceutical technology have significantly accelerated progress in this field. Strategies such as structural modification, cyclization, nanoformulation, intelligent delivery systems, and artificial intelligence-assisted peptide design have improved peptide stability, targeting efficiency, pharmacokinetic properties, and production feasibility. These technological innovations provide new opportunities to overcome the major limitations associated with marine peptide therapeutics. This review systematically summarizes the sources, structural characteristics, extraction and purification methods, molecular mechanisms, and in vitro and in vivo anti-CRC activities of marine-derived peptides. In addition, the major translational challenges and current technological solutions are critically discussed, with particular emphasis on the integration of multidisciplinary approaches for the development of next-generation marine peptide-based therapeutics for colorectal cancer.