# Attenuated Bacteria‐Based Tumor Therapy: Clinical Application Risks, Marketing Approval Restrictions, and Coping Strategies

## TL;DR

This review discusses the use of genetically modified bacteria for cancer treatment, focusing on safety, efficacy, and regulatory challenges to help advance this promising therapy.

## Contribution

The paper provides a comprehensive overview of strategies to improve safety, efficacy, and regulatory approval for attenuated bacteria-based cancer therapies.

## Key findings

- Genetic modifications can enhance safety and anti-tumor effects of attenuated bacteria.
- Multimodal imaging enables real-time monitoring of bacterial behavior during treatment.
- Regulatory pathways and production optimization are critical for clinical translation.

## Abstract

Bacteria‐based cancer therapy is a promising cancer treatment strategy that utilizes genetically engineered attenuated bacteria to specifically target tumor tissues, directly kill cancer cells, or activate the host's immune response. Engineering modifications of attenuated bacteria can achieve more effective anti‐tumor effects, and consequently, a number of clinical trials have been carried out. However, the clinical translation of attenuated bacteria faces multiple challenges, including safety risks, fluctuating therapeutic efficacy, difficulties in vivo monitoring, complex production quality control, and lack of regulatory approval standards. This review mainly summarizes five aspects of bacterial cancer therapy: the safety risks and attenuation strategies, the regulation of therapeutic stability, bacterial in vivo imaging technologies, the optimization of bacterial production processes, and market approval pathways. It aims to precisely control bacterial behavior through genetic circuits and enable real‐time monitoring of the treatment process by means of multimodal imaging, ultimately promoting the clinical translation of attenuated bacterial therapy.

This review comprehensively overviews attenuated bacteria‐based tumor therapy, highlighting key methodologies and recent progress. It examines strategies for enhancing safety, stabilizing efficacy, optimizing manufacturing, and navigating regulatory pathways. We aim to guide scientists and microbiologists in engineering optimal attenuated bacteria, while aiding in overcoming current obstacles to accelerate the clinical translation of this therapeutic approach.