Context‑dependent targeting of thioredoxin reductase 1 in cancer: a mechanistic review

Targeting the cytosolic selenoprotein thioredoxin reductase 1 (TrxR1, also named TXNRD1) has emerged as a promis­ing strategy to exploit redox vulnerabilities in cancer. How­ever, both preclinical observations and recent mechanistic studies indicate that TrxR1 inhibition can have context‑de­pendent outcomes. This article synthesizes a mechanistic framework linking cytosolic redox buffering, proteostasis, receptor tyrosine kinase (RTK) signaling, and immune sur­veillance with treatment responses. It highlights the dual functional roles of the TrxR1-substrate TXNL1 (also named TRP32), discusses intracellular transcriptional crosstalk shaping treatment sensitivity, and outlines potential combi­nation strategies with RTK modulators.

Magy Onkol 70:128- 135, 2026