Bacterial-directed enzyme prodrug therapy (BDEPT) is an emerging form of treatment for cancer. It is a biphasic variant of gene therapy in which a bacterium, armed with an enzyme that can convert an inert prodrug into a cytotoxic compound, induces tumour cell death following tumour-specific prodrug activation. BDEPT combines the innate ability of bacteria to selectively proliferate in tumours, with the capacity of prodrugs to undergo contained, compartmentalised conversion into active metabolites in vivo. Although BDEPT has undergone clinical testing, it has received limited clinical exposure, and has yet to achieve regulatory approval. In this article, we review BDEPT from the system designer's perspective, and provide detailed commentary on how the designer should strategize its development de novo. We report on contemporary advancements in this field which aim to enhance BDEPT in terms of safety and efficacy. Finally, we discuss clinical and regulatory barriers facing BDEPT, and propose promising approaches through which these hurdles may best be tackled.

细菌定向酶前药疗法（BDEPT）是一种新兴的癌症治疗方法。它是基因治疗的两相变体，其中一种细菌携带一种可以将惰性前药转化为细胞毒性化合物的酶，可以在肿瘤特异性前药激活后诱导肿瘤细胞死亡。BDEPT结合了细菌固有的在肿瘤中选择性增殖的能力，以及前药在体内进行封闭，分隔转化为活性代谢物的能力。尽管BDEPT已通过临床测试，但其临床暴露量有限，并且尚未获得监管机构的批准。在本文中，我们从系统设计者的角度回顾了BDEPT，并提供了有关设计者应如何制定战略计划的详细评论。从头开始。我们报告了该领域的当代进展，旨在提高BDEPT的安全性和功效。最后，我们讨论了BDEPT面临的临床和法规障碍，并提出了有希望的方法来最好地解决这些障碍。