Bioreductive prodrugs as cancer therapeutics: targeting tumor hypoxia / 癌症
Chinese Journal of Cancer
;
(12): 80-86, 2014.
Article
in English
| WPRIM
| ID: wpr-320564
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pathology
/
Pharmacology
/
Phosphoramide Mustards
/
Aziridines
/
Triazines
/
Prodrugs
/
Molecular Structure
/
Cell Hypoxia
/
Chemistry
/
Anthraquinones
Limits:
Humans
Language:
English
Journal:
Chinese Journal of Cancer
Year:
2014
Type:
Article
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