Thioredoxin signaling as a target for cancer therapy.
Thioredoxin (Trx) family members play critical roles in the regulation of cellular redox homeostasis. Cancer cells exist in a stressed environment and rely on the Trxs for protection against stress-disregulated redox signaling. The most extensively studied member of the family is Trx-1 whose levels are increased in many human cancers most likely in direct response to stress. Trx-1 contributes to many of the hallmarks of cancer including increased proliferation, resistance to cell death and increased angiogenesis. Trx-1 is a validated cancer drug target associated with aggressive tumor growth, resistance to standard therapy and decreased patient survival. A surrogate target for Trx-1 may be thioredoxin reductase (TR). Drugs that inhibit Trx-1 and TR are in clinical development with early promising results.
Powis
Garth
G
Department of Experimental Therapeutics, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030-4009, USA. gpowis@mdanderson.org
Kirkpatrick
D Lynn
DL
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000503:physiopathology; D010084:Oxidation-Reduction; D015398:Signal Transduction / Q000187:drug effects; D013880:Thioredoxin-Disulfide Reductase / Q000187:drug effects* / Q000378:metabolism; D013879:Thioredoxins / Q000187:drug effects* / Q000378:metabolism
D000970:Antineoplastic Agents; C491203:TXN protein, human; D013879:Thioredoxins; D013880:Thioredoxin-Disulfide Reductase