Zahedifard Zahra, Mahmoodi Shirin, Ghasemian Abdolmajid
Department of Medical Biotechnology, School of Medicine, Fasa University of Medical Sciences, Fasa, Iran.
Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran.
Biotechnol Appl Biochem. 2025 Feb 21. doi: 10.1002/bab.2738.
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 and P), and Listeria monocytogenes Lm-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.
作为全球死亡的一个重要原因，癌症也具有经济影响。在癌症治疗时代，减轻副作用和成本以及克服耐药性至关重要。微生物物种可在肿瘤微环境中生长，并通过直接杀死肿瘤细胞和免疫调节作用来抑制癌症生长。尽管微生物群或其产物已显示出抗癌作用，但在某些个体中充当病原体并产生副作用的可能性是一种风险。因此，已开发出几种基因改造/工程细菌（GEB）来实现这一目标，它们具有诊断、选择性靶向和破坏癌症的能力。此外，与野生型相比，GEB有望成为更高效、更安全、更具渗透性、成本更低且侵入性更小的诊疗方法。已开发出潜在的GEB菌株，如大肠杆菌（Nissle 1917和MG1655）、鼠伤寒沙门氏菌YB1 SL7207（aroA基因缺失）、VNP20009（∆msbB/∆purI）和ΔppGpp（P和P）以及单核细胞增生李斯特菌Lm-LLO来对抗癌细胞。当与传统治疗联合使用时，GEB可显著提高抗癌治疗效果。此外，公众接受度、最佳时间、持续时间、剂量以及菌株鉴定、与其他菌株和宿主细胞的相互作用、疗效、安全性和质量以及潜在风险和伦理困境等都是主要挑战。
