Exploring the advancements and applications of bacterial protein therapeutics in the treatment of colorectal cancer: A comprehensive review

Colorectal cancer (CRC) remains a major global health burden, and limitations associated with conventional chemotherapy, including systemic toxicity, drug resistance, and non-specific targeting necessitate the development of safer and more selective therapeutic strategies. Increasing evidence indicates that bacterial proteins and microbial metabolites can modulate host immune responses and tumor signaling pathways, particularly through interactions with toll-like receptors (TLRs) and gut microbiota mediated immune regulation. The present review systematically analyzes recent advances in bacterial protein based therapeutics for CRC, focusing on their mechanisms of action, including apoptosis induction, inhibition of angiogenesis, immune modulation, and disruption of tumor cell metabolism. Literature from major databases such as Scopus, Web of Science, Embase, and Medline was critically evaluated to summarize experimental and emerging translational evidence on bacterial proteins, bacteriocins, and microbial peptides with anticancer potential. The analysis highlights that several bacterial-derived proteins, including bacteriocins, cytotoxic peptides, and probiotic metabolites demonstrate promising in vitro and preclinical anticancer activity against CRC cell lines through immune activation and targeted cytotoxic mechanisms. Importantly, this review identifies current knowledge gaps in clinical translation, pharmacokinetics, targeted delivery, and large-scale production of bacterial protein therapeutics. Overall, the findings underscore the growing therapeutic relevance of microbiota-derived biomolecules and emphasize their potential to serve as novel microbe-based anticancer agents within the emerging field of microbiome-guided oncology.