Engineered Bacteria for Cancer Therapy: Synergistic Innovations in Synthetic Biology and Materials Science
Cancer remains the second leading cause of death globally, with approximately 20 million new cases and 9.7 million deaths in 2022. Traditional therapies—surgery, radiotherapy, and chemotherapy—suffer from poor targeting, systemic toxicity, drug resistance, and recurrence. Immunotherapy, while promising, achieves low patient response rates. Bacterial therapies exploit the hypoxic and immunosuppressive tumor microenvironment (TME) to selectively colonize and penetrate tumors, eliciting innate and adaptive immune responses. However, natural bacteria exhibit intrinsic virulence and uncontrolled replication, limiting clinical translation. This review examines recent advances in engineered bacteria for anti-tumor therapy, focusing on synthetic biology modifications and material science interventions that enhance safety and efficacy. Engineered bacteria can synthesize and release payloads in response to internal or external stimuli, leading to tumor regression and inhibition of recurrence. We discuss advantageous features, modification strategies, and remaining challenges, including precise spatiotemporal control, immunogenicity management, and scalable manufacturing. The integration of synthetic biology with materials science offers a viable pathway to develop low-toxicity, multifunctional bacterial therapeutics capable of overcoming the limitations of conventional and immunotherapeutic approaches.