Bacteria Yield Diverse Anticancer Metabolites and Engineered Platforms for Tumor-Targeted Therapies

Cancer remains a leading cause of mortality, necessitating continuous discovery of novel therapeutic agents. Current standard-of-care treatments often face challenges like drug resistance, systemic toxicity, and limited selectivity for tumor cells. Bacteria represent a vast, underexplored reservoir of bioactive compounds with significant anticancer potential, offering unique chemical structures and mechanisms of action that could overcome these limitations. This review explores their role in addressing the urgent need for new oncology strategies.

This comprehensive review synthesized current literature on bacteria as anticancer agents, focusing on bioactive metabolites, engineered bacterial platforms, and their translational mechanisms. Researchers systematically summarized bacterial sources (e.g., actinomycetes, Bacillus, Pseudomonas, marine-derived species), identified diverse metabolite classes (polyketides, peptides, alkaloids, proteins), and elucidated their molecular mechanisms of action. The review also covered advances in metagenomics, genome mining, and synthetic biology for drug discovery and the development of tumor-targeting bacterial platforms.

The review highlighted that numerous bacterial taxa produce structurally diverse metabolites exhibiting potent anticancer activities. These compounds demonstrate cytotoxic, cytostatic, pro-apoptotic, immunomodulatory, and anti-angiogenic effects against cancer cells. Clinically established agents like actinomycin D and bleomycin underscore the therapeutic relevance of bacterial natural products. Key mechanisms include DNA intercalation, induction of apoptosis, cell cycle arrest, metabolic disruption, and modulation of the tumor microenvironment.

Advances in metagenomics and synthetic biology have enabled the identification and activation of previously silent biosynthetic gene clusters, significantly enhancing drug discovery potential.

Engineered bacterial platforms can selectively colonize tumors, deliver therapeutic molecules, and activate prodrug therapies directly within the tumor microenvironment. The breadth of bacterial-derived compounds and their multifaceted actions suggest a promising frontier for oncology.