Exploiting Salmonella typhimurium as a novel cancer therapeutic agent: from tumor colonization to metabolic engineering.

Cancer treatment mediated by bacteria, also known as Bacteria-mediated cancer therapy (BMCT), has emerged as a promising strategy that overcomes several limitations of conventional cancer treatments by exploiting the natural tumor-targeting ability of bacteria. Among them, Salmonella typhimurium has gained particular attention due to its intrinsic capacity to colonize hypoxic and nutrient-deprived regions of tumors, secrete cytotoxins, and activate host immune responses. This review, along with summarizing these mechanisms, uniquely integrates the diverse anticancer mechanisms of S. typhimurium, such as apoptosis and autophagy induction, immune modulation, nutrient competition, and tumor colonization, which collectively contribute to tumor regression. We discuss the recent advances in metabolic engineering and synthetic biology to provide a unified perspective on how engineered strains achieve enhanced specificity, biosafety, and controlled intratumoral payload delivery. We also critically evaluate the current limitations and translational challenges of BMCT, emphasizing that bacteria-based therapies only complement and not replace existing cancer treatments.