Cellular redox regulation pathways (None)

Cellular redox regulation pathways encompass a complex network of enzymatic and non-enzymatic systems dedicated to maintaining the balance between reactive oxygen species (ROS) and antioxidant defenses, a state known as redox homeostasis [1, 11]. Key components include the glutathione (GSH) and thioredoxin (Trx) systems, as well as the Nrf2-Keap1 signaling axis, which collectively regulate cellular responses to oxidative stress [2, 12]. In many diseases, particularly cancer, these pathways are dysregulated; tumor cells often exhibit elevated ROS levels and upregulate antioxidant systems to survive, creating a therapeutic vulnerability [1, 5]. Drugs targeting these pathways aim to either overwhelm the antioxidant capacity of cancer cells to induce apoptosis or activate cytoprotective mechanisms in healthy tissues to prevent damage [3, 8]. Examples of such agents include thioredoxin inhibitors like PX-12 and Nrf2 activators like bardoxolone methyl [1, 7]. However, the dual role of ROS in both signaling and damage presents significant challenges, as excessive modulation can lead to systemic toxicity or unintended promotion of disease progression [5, 14].

Other names

Redox homeostasis pathwaysAntioxidant defense systemsCellular redox signalingRedox control systems

Drugs targeting these pathways operate by modulating the balance between pro-oxidants and antioxidants. This includes inhibiting key antioxidant enzymes such as thioredoxin reductase or glutathione reductase to increase ROS levels in cancer cells, activating the Nrf2 transcription factor to enhance cytoprotective gene expression, or using pro-oxidant agents like arsenic trioxide to directly induce oxidative stress and apoptosis [1, 3, 5, 9].