Current status and future perspectives of multi-modal bacteria-based cancer therapies

Shuai Fan , Siyu Zhu , Wenyu Wang , Yuetong Liu , Yutong Zhou , Hao Li , Bofeng Liu , Qin Xia , Lili Huang , Lei Dong

Clinical and Translational Medicine ›› 2025, Vol. 15 ›› Issue (10) : e70485

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Clinical and Translational Medicine ›› 2025, Vol. 15 ›› Issue (10) : e70485 DOI: 10.1002/ctm2.70485
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Current status and future perspectives of multi-modal bacteria-based cancer therapies

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Abstract

Background: Targeted drug delivery systems have garnered increasing research interest in cancer threapy. Bacteria have emerged as a promising vehicle due to their innate ability to the tumour microenvironment (TME) and their intrinsic immune-stimulating properties. This review explores the application of bacteria in oncology, emphasizing the tumour-targeting behaviour of specific strains, their immunomodulatory functions, and their potential as delivery platforms for the controlled release of therapeutic agents.

Main text: This review synthesizes recent advances in bacteria-mediated cancer therapy, focusing on the mechanisms underlying bacterial targeting of hypoxic and immunosuppressive regions within the tumor microenvironment (TME). We discuss how genetic modification has been employed to design recombinant bacterial strains with enhanced tumor specificity and amplified therapeutic effects. Furthermore, the integration of bacteria with nanotechnology has facilitated the development of hybrid systems capable of targeted drug delivery and triggered-release mechanisms. The combination of bacterial therapy with other treatment modalities—such as photodynamic (PDT) and sonodynamic therapies (SDT)—is also examined, emphasizing their synergistic potential in overcoming tumor heterogeneity and enhancing anti-tumor immunity. Finally, we survey the current clinical progress of bacteria-based therapeutics and offer perspectives on the future role of artificial intelligence (AI) in improving the design and application of these living medicines.

Conclusions: Bacteria-based delivery systems represent a multifunctional and innovative strategy in the evolution of targeted cancer therapies. Through genetic modification and nanobiotechnology approaches, bacteria can be customized to mediate multi-effect synergistic treatments for cancer, enhancing the precision, safety, and efficacy of cancer therapies. With the ongoing integration of advanced technologies, including AI, there is great potential to overcome existing limitations and accelerate the clinical translation of bacterial anticancer therapies. This interdisciplinary effort is poised to open new avenues for next-generation cancer treatments and lay the foundation for future directions in cancer research and therapeutic practice.

Keywords

bacteria / cancer / TME / genetic modification / nanotechnology / synergistic therapy

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Shuai Fan, Siyu Zhu, Wenyu Wang, Yuetong Liu, Yutong Zhou, Hao Li, Bofeng Liu, Qin Xia, Lili Huang, Lei Dong. Current status and future perspectives of multi-modal bacteria-based cancer therapies. Clinical and Translational Medicine, 2025, 15(10): e70485 DOI:10.1002/ctm2.70485

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