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 language | English (US) |
|---|---|
| Pages (from-to) | 3013-3069 |
| Number of pages | 57 |
| Journal | Antioxidants and Redox Signaling |
| Volume | 11 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 1 2009 |
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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 journal › Article
}
TY - JOUR
T1 - Redox-directed cancer therapeutics
T2 - Molecular mechanisms and opportunities
AU - Wondrak, Georg T
PY - 2009/12/1
Y1 - 2009/12/1
N2 - 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.
AB - 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.
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U2 - 10.1089/ars.2009.2541
DO - 10.1089/ars.2009.2541
M3 - Article
VL - 11
SP - 3013
EP - 3069
JO - Antioxidants and Redox Signaling
JF - Antioxidants and Redox Signaling
SN - 1523-0864
IS - 12
ER -