Engineering Bacteria as Living Therapeutics in Cancer Therapy

Through synthetic biology approaches, natural bacteria can be genetically programmed into multifunctional living therapeutics. These engineered bacteria are capable of secreting anti‐tumor factors, displaying tumor‐associated antigens on their surface, or undergoing programmed self‐lysis to release therapeutic cargo. These functions are precisely orchestrated by the genetic circuits, enabling spatiotemporal control of therapeutic response. Abstract Cancer is the second‐leading cause of death globally, yet traditional therapies like chemotherapy face significant limitations. Recent advances in synthetic biology enable the design of various genetic circuits and the reprogramming of biological systems. Collectively, these efforts have led to the repurposing of engineered bacteria as therapeutics to achieve tumor targeting, tumor microenvironment modulation, and anticancer drug release. Here, these recent efforts are reviewed and discussed the challenges and future opportunities. Through synthetic biology approaches, natural bacteria can be genetically programmed into multifunctional living therapeutics. These engineered bacteria are capable of secreting anti-tumor factors, displaying tumor-associated antigens on their surface, or undergoing programmed self-lysis to release therapeutic cargo. These functions are precisely orchestrated by the genetic circuits, enabling spatiotemporal control of therapeutic response. Abstract Cancer is the second-leading cause of death globally, yet traditional therapies like chemotherapy face significant limitations. Recent advances in synthetic biology enable the design of various genetic circuits and the reprogramming of biological systems. Collectively, these efforts have led to the repurposing of engineered bacteria as therapeutics to achieve tumor targeting, tumor microenvironment modulation, and anticancer drug release. Here, these recent efforts are reviewed and discussed the challenges and future opportunities. Advanced Science, Volume 12, Issue 42, November 13, 2025.