Experimental therapeutics: targeting the redox Achilles heel of cancer.

Abstract

Reactive oxygen species (ROS) have recently emerged as promising targets for anticancer drug discovery. Constitutively elevated levels of cellular oxidative stress and dependence on mitogenic and anti-apoptotic ROS signaling represent a specific vulnerability of malignant cells that can be selectively targeted by novel pro- and antioxidant redox chemotherapeutics. This review discusses small-molecule anticancer redox drugs currently in various phases of preclinical and clinical development that are characterized by their unique mechanism of action, including small-molecule superoxide dismutase and catalase mimetics, bioreductively activated pro-oxidant redox catalysts, metal-based pro-oxidants, hypoxia-selective free radical precursors, and specific antagonists of the cancer cell antioxidant glutathione or thioredoxin redox systems. Based on ongoing redox biomarker discovery and validation, future redox phenotyping and genotyping may guide the selection of novel redox chemotherapeutics that efficiently target the redox Achilles heel of the individual tumor.

• Authors: Christopher M Cabello, Warner B Bair 3rd, Georg T Wondrak
• Journal: Current opinion in investigational drugs (London, England : 2000) (Curr Opin Investig Drugs) Vol. 8 Issue 12 Pg. 1022-37 (Dec 2007) ISSN: 1472-4472 [Print] England
• PMID: 18058573 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Review)

Chemical References

• Antineoplastic Agents
• Antioxidants
• Reactive Oxygen Species

Topics

• Animals
• Antineoplastic Agents (therapeutic use)
• Antioxidants (chemistry, metabolism)
• Feasibility Studies
• Humans
• Models, Biological
• Neoplasms (drug therapy, genetics, metabolism, pathology)
• Oxidation-Reduction
• Oxidative Stress
• Reactive Oxygen Species (chemistry, metabolism)
• Signal Transduction (drug effects)