Oxidative Stress in Cancer

• Published in: Cancer cell Vol. 38; no. 2; pp. 167 - 197
• Main Authors: Hayes, John D., Dinkova-Kostova, Albena T., Tew, Kenneth D.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.08.2020
• Subjects: adaptation; Animals; antioxidant; Antioxidants - metabolism; AP-1; Apoptosis - genetics; BACH1; dormant cancer cell; Energy Metabolism - genetics; folate metabolism; FOXO; Glucose - metabolism; glutathione; HIF-1alpha; HSF1; Humans; initiation; metastasis; NADP - metabolism; NADPH generation; Neoplasms - genetics; Neoplasms - metabolism; NF-κB; NRF2; Oxidative Stress; pentose phosphate pathway; PGC-1alpha; progression; reactive oxygen species; Reactive Oxygen Species - metabolism; recurrent disease; redox signaling; reductive glutamine metabolism; thioredoxin; TP53; tumorigenesis; thioredoxin; glutathione; adaptation; progression; BACH1; AP-1; reductive glutamine metabolism; NF-κB; redox signaling; initiation; NRF2; metastasis; reactive oxygen species; HSF1; tumorigenesis; folate metabolism; dormant cancer cell; FOXO; antioxidant; NADPH generation; HIF-1alpha; recurrent disease; pentose phosphate pathway; PGC-1alpha; TP53; oxidative stress
• ISSN: 1535-6108; 1878-3686; 1878-3686
• DOI: 10.1016/j.ccell.2020.06.001

Contingent upon concentration, reactive oxygen species (ROS) influence cancer evolution in apparently contradictory ways, either initiating/stimulating tumorigenesis and supporting transformation/proliferation of cancer cells or causing cell death. To accommodate high ROS levels, tumor cells modify sulfur-based metabolism, NADPH generation, and the activity of antioxidant transcription factors. During initiation, genetic changes enable cell survival under high ROS levels by activating antioxidant transcription factors or increasing NADPH via the pentose phosphate pathway (PPP). During progression and metastasis, tumor cells adapt to oxidative stress by increasing NADPH in various ways, including activation of AMPK, the PPP, and reductive glutamine and folate metabolism.