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Investigational Hypoxia-Activated Prodrugs: Making Sense of Future Development

[ Vol. 20 , Issue. 6 ]

Author(s):

Min-Xia Su, Le-Le Zhang, Zhang-Jian Huang, Jia-Jie Shi and Jin-Jian Lu*   Pages 668 - 678 ( 11 )

Abstract:


Hypoxia, which occurs in most cancer cases, disrupts the efficacy of anticarcinogens. Fortunately, hypoxia itself is a potential target for cancer treatment. Hypoxia-activated prodrugs (HAPs) can be selectively activated by reductase under hypoxia. Some promising HAPs have been already achieved, and many clinical trials of HAPs in different types of cancer are ongoing. However, none of them has been approved in clinic to date. From the studies on HAPs began, some achievements are obtained but more challenges are put forward. In this paper, we reviewed the research progress of HAPs to discuss the strategies for HAPs development. According to the research status and results of these studies, administration pattern, reductase activity, and patient selection need to be taken into consideration to further improve the efficacy of existing HAPs. As the requirement of new drug research and development, design of optimal preclinical models and clinical trials are quite important in HAPs development, while different drug delivery systems and anticancer drugs with different mechanisms can be sources of novel HAPs.

Keywords:

Hypoxia-activated prodrug, topoisomerase II inhibitors, DNA alkylating agents, targeted drugs, reductase activity, patient selection.

Affiliation:

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao

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