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Review
. 2025 Sep;21(35):e2505651.
doi: 10.1002/smll.202505651. Epub 2025 Jul 11.

Targeting Intratumoral Bacteria for Cancer Treatment

Affiliations
Review

Targeting Intratumoral Bacteria for Cancer Treatment

Jianbin Shi et al. Small. 2025 Sep.

Abstract

Intratumoral bacteria have emerged as critical modulators of cancer biology and therapeutic outcomes. Substantial evidence has demonstrated that tumors harbor diverse bacterial communities capable of interacting with both cancer cells and host immunity to influence tumor progression and treatment responses. These bacteria adapt to the immunosuppressive, hypoxic, and acidic tumor microenvironment, leveraging these conditions to thrive. This review provides an overview of intratumoral bacteria, focusing on their origins, colonization mechanisms, detection methods, and roles in tumor development and metastasis. Furthermore, their dual impact on therapeutic efficacy is discussed, enhancing anti-tumor immunity or conferring treatment resistance. Critically, emerging targeting strategies including engineered bacteria design, vaccine strategies, oncolytic therapy, antibiotics mediated nano strategies, and regulating intratumoral bacteria abundance are also discussed. Despite translational promise, key challenges remain in safety validation, targeting precision, and deciphering complex bacteria-tumor-immune crosstalk. By elucidating the multifaceted biology of intratumoral bacteria, the review aims to accelerate clinical translation and inspire innovative cancer therapeutics.

Keywords: cancer metastasis; cancer progression; intratumoral bacteria; prospective and challenges; targeting therapy.

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