Research ArticleCancer

Irreversible inhibition of cytosolic thioredoxin reductase 1 as a mechanistic basis for anticancer therapy

See allHide authors and affiliations

Science Translational Medicine  14 Feb 2018:
Vol. 10, Issue 428, eaaf7444
DOI: 10.1126/scitranslmed.aaf7444

A safer way to reduce tumors

Oxidative stress is a common feature of the tumor microenvironment, and the tumor cells adapt to it by activating the glutathione and thioredoxin antioxidant pathways. However, noncancer cells also require these pathways for survival, and inhibiting both pathways simultaneously can cause unacceptable toxicity. Instead, Stafford et al. decided to target the thioredoxin pathway alone in an effort to kill cancer cells with less collateral damage. Through a large-scale screening effort, the authors identified candidate inhibitors of the enzyme thioredoxin reductase 1 and then demonstrated their biological effects and anticancer efficacy in vitro and in multiple mouse models.

View Full Text

Stay Connected to Science Translational Medicine