Genetically Engineered Bacteria as a Promising Therapeutic Strategy Against Cancer: A Comprehensive Review

As a significant cause of global mortality, the cancer has also economic impacts. In the era of cancer therapy, mitigating side effects and costs and overcoming drug resistance is crucial. Microbial species can grow inside the tumor microenvironment and inhibit cancer growth through direct killing of tumor cells and immunoregulatory effects. Although microbiota or their products have demonstrated anticancer effects, the possibility of acting as pathogens and exerting side effects in certain individuals is a risk. Hence, several genetically modified/engineered bacteria (GEB) have been developed to this aim with ability of diagnosing and selective targeting and destruction of cancers. Additionally, GEB are expected to be considerably more efficient, safer, more permeable, less costly, and less invasive theranostic approaches compared to wild types. Potential GEB strains such as Escherichia coli (Nissle 1917, and MG1655), Salmonella typhimurium YB1 SL7207 (aroA gene deletion), VNP20009 (∆msbB/∆purI) and ΔppGpp (P_Tet and P_BAD), and Listeria monocytogenes Lm^at-LLO have been developed to combat cancer cells. When used in tandem with conventional treatments, GEB substantially improve the efficacy of anticancer therapy outcomes. In addition, public acceptance, optimal timing (s), duration (s), dose (s), and strains identification, interactions with other strains and the host cells, efficacy, safety and quality, and potential risks and ethical dilemmas include major challenges.