Details

Autor(en) / Beteiligte

• Samarin, Jana
• Fabrowski, Piotr
• Kurilov, Roman
• Nuskova, Hana
• Hummel-Eisenbeiss, Johanna
• Pink, Hannelore
• Li, Nan
• Weru, Vivienn
• Alborzinia, Hamed
• Yildiz, Umut
• Grob, Laura
• Taubert, Minerva
• Czech, Marie
• Morgen, Michael
• Brandstädter, Christina
• Becker, Katja
• Mao, Lianghao
• Jayavelu, Ashok Kumar
• Goncalves, Angela
• Uhrig, Ulrike
• Seiler, Jeanette
• Lyu, Yanhong
• Diederichs, Sven
• Klingmüller, Ursula
• Muckenthaler, Martina
• Kopp-Schneider, Annette
• Teleman, Aurelio
• Miller, Aubry K.
• Gunkel, Nikolas

Titel

Low level of antioxidant capacity biomarkers but not target overexpression predicts vulnerability to ROS-inducing drugs

Ist Teil von

• Redox biology, 2023-06, Vol.62, p.102639-102639, Article 102639

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2023

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Despite a strong rationale for why cancer cells are susceptible to redox-targeting drugs, such drugs often face tumor resistance or dose-limiting toxicity in preclinical and clinical studies. An important reason is the lack of specific biomarkers to better select susceptible cancer entities and stratify patients. Using a large panel of lung cancer cell lines, we identified a set of “antioxidant-capacity” biomarkers (ACB), which were tightly repressed, partly by STAT3 and STAT5A/B in sensitive cells, rendering them susceptible to multiple redox-targeting and ferroptosis-inducing drugs. Contrary to expectation, constitutively low ACB expression was not associated with an increased steady state level of reactive oxygen species (ROS) but a high level of nitric oxide, which is required to sustain high replication rates. Using ACBs, we identified cancer entities with a high percentage of patients with favorable ACB expression pattern, making it likely that more responders to ROS-inducing drugs could be stratified for clinical trials.