Redox-directed cancer therapeutics

Molecular mechanisms and opportunities

Research output: Contribution to journalArticle

310 Citations (Scopus)

Abstract

Redox dysregulation originating from metabolic alterations and dependence on mitogenic and survival signaling through reactive oxygen species represents a specific vulnerability of malignant cells that can be selectively targeted by redox chemotherapeutics. This review will present an update on drug discovery, target identification, and mechanisms of action of experimental redox chemotherapeutics with a focus on pro-and antioxidant redox modulators now in advanced phases of preclinal and clinical development. Recent research indicates that numerous oncogenes and tumor suppressor genes exert their functions in part through redox mechanisms amenable to pharmacological intervention by redox chemotherapeutics. The pleiotropic action of many redox chemotherapeutics that involves simultaneous modulation of multiple redox sensitive targets can overcome cancer cell drug resistance originating from redundancy of oncogenic signaling and rapid mutation. Moreover, some redox chemotherapeutics may function according to the concept of synthetic lethality (i.e., drug cytotoxicity is confined to cancer cells that display loss of function mutations in tumor suppressor genes or upregulation of oncogene expression). The impressive number of ongoing clinical trials that examine therapeutic performance of novel redox drugs in cancer patients demonstrates that redox chemotherapy has made the crucial transition from bench to bedside. Antioxid. Redox Signal. 11, 3013-3069.

Original languageEnglish (US)
Pages (from-to)3013-3069
Number of pages57
JournalAntioxidants and Redox Signaling
Volume11
Issue number12
DOIs
StatePublished - Dec 1 2009

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Oxidation-Reduction
Neoplasms
Therapeutics
Tumor Suppressor Genes
Oncogenes
Tumors
Genes
Cells
Pharmaceutical Preparations
Mutation
Chemotherapy
Drug Discovery
Cytotoxicity
Drug Resistance
Modulators
Redundancy
Reactive Oxygen Species
Up-Regulation
Antioxidants
Modulation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Physiology
  • Clinical Biochemistry

Cite this

Redox-directed cancer therapeutics : Molecular mechanisms and opportunities. / Wondrak, Georg T.

In: Antioxidants and Redox Signaling, Vol. 11, No. 12, 01.12.2009, p. 3013-3069.

Research output: Contribution to journalArticle

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