Engineered bacteria for cancer therapy: Advancements, challenges, and future directions

Recent advancements in cancer therapeutics, including targeted therapies and immunotherapies, have significantly improved treatment outcomes but remain limited by challenges such as off-target toxicity, poor penetration into deep tumor tissues, and the emergence of drug resistance. Engineered bacteria-based cancer therapies present a novel and versatile approach to address these limitations. Leveraging their ability to selectively colonize tumor microenvironments, bacteria can elicit antitumor immune responses and serve as platforms for the localized delivery of therapeutic agents. Through genetic engineering and synthetic biology, bacteria can be programmed to produce anticancer payloads tailored to clinical needs. This review highlights recent progress in the design and application of engineered bacteria for cancer therapy, emphasizing innovative strategies to enhance therapeutic delivery and efficacy. In addition, we discuss the integration of bacteria-based approaches with conventional therapies to overcome intratumor heterogeneity and improve treatment outcomes. Finally, we discuss insights from past and ongoing clinical trials of tumor-targeting bacteria, alongside challenges that must be surmounted to realize their full therapeutic promise.