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Chinese journal of cancer
Feb, 2014;33 (2): 80-6.

Bioreductive prodrugs as cancer therapeutics: targeting tumor hypoxia.

Christopher P Guise, Alexandra M Mowday, Amir Ashoorzadeh, Ran Yuan, Wan-Hua Lin, Dong-Hai Wu, Jeff B Smaill, Adam V Patterson, Ke Ding
Author Information
  1. Christopher P Guise: Auckland Cancer Society Research Centre, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand. ding_ke@gibh.ac.cn.
PMID: 23845143 DOI: 10.5732/cjc.012.10285

Abstract

hypoxia, a state of low oxygen, is a common feature of solid tumors and is associated with disease progression as well as resistance to radiotherapy and certain chemotherapeutic drugs. Hypoxic regions in tumors, therefore, represent attractive targets for cancer therapy. To date, five distinct classes of bioreactive prodrugs have been developed to target Hypoxic cells in solid tumors. These hypoxia-activated prodrugs, including nitro compounds, N-oxides, quinones, and metal complexes, generally share a common mechanism of activation whereby they are reduced by intracellular oxidoreductases in an oxygen-sensitive manner to form cytotoxins. Several examples including PR-104, TH-302, and EO9 are currently undergoing phase II and phase III clinical evaluation. In this review, we discuss the nature of tumor hypoxia as a therapeutic target, focusing on the development of bioreductive prodrugs. We also describe the current knowledge of how each prodrug class is activated and detail the clinical progress of leading examples.

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MeSH Term

Anthraquinones
Antineoplastic Agents
Aziridines
Cell Hypoxia
Humans
Indolequinones
Molecular Structure
NAD(P)H Dehydrogenase (Quinone)
Neoplasms
Nitrogen Mustard Compounds
Nitroimidazoles
Phosphoramide Mustards
Prodrugs
Tirapazamine
Triazines

Chemicals

Anthraquinones
Antineoplastic Agents
Aziridines
Indolequinones
Nitrogen Mustard Compounds
Nitroimidazoles
PR-104
Phosphoramide Mustards
Prodrugs
TH 302
Triazines
Tirapazamine
AQ4N
NAD(P)H Dehydrogenase (Quinone)
NQO1 protein, human
apaziquone
Journal Article Research Support, Non-U.S. Gov't Review
Article has an altmetric score of 3

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