4.7 Review

Designer bacteria as intratumoural enzyme biofactories

期刊

ADVANCED DRUG DELIVERY REVIEWS
卷 118, 期 -, 页码 8-23

出版社

ELSEVIER SCIENCE BV
DOI: 10.1016/j.addr.2017.09.012

关键词

Tumour; DEPT; Prodrug; Cancer; Chemotherapy; Drug design; Synthetic biology; Targeted; Translational research; R&D

资金

  1. Irish Cancer Society [PCI12TAN]
  2. Science Foundation Ireland [15/CDA/3630]
  3. European Commission Seventh Framework Program [PIAP-GA-2013-612219-VIP]
  4. Breakthrough Cancer Research
  5. Science Foundation Ireland (SFI) [15/CDA/3630] Funding Source: Science Foundation Ireland (SFI)

向作者/读者索取更多资源

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. (C) 2017 Elsevier B.V. All rights reserved.

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