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

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 stra...

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Main Authors: Samarin, Jana (Author) , Fabrowski, Piotr (Author) , Kurilov, Roman (Author) , Nůsková, Hana (Author) , Hummel-Eisenbeiß, Johanna (Author) , Pink, Hannelore (Author) , Li, Nan (Author) , Weru, Vivienn (Author) , Alborzinia, Hamed (Author) , Yildiz, Umut (Author) , Grob, Laura (Author) , Täubert, Minerva Jazmin (Author) , Czech, Marie (Author) , Morgen, Michael (Author) , Brandstädter, Christina (Author) , Becker, Katja (Author) , Mao, Lianghao (Author) , Jayavelu, Ashok Kumar (Author) , Goncalves, Angela (Author) , Uhrig, Ulrike (Author) , Seiler, Jeanette (Author) , Lyu, Yanhong (Author) , Diederichs, Sven (Author) , Klingmüller, Ursula (Author) , Muckenthaler, Martina (Author) , Kopp-Schneider, Annette (Author) , Teleman, Aurelio A. (Author) , Miller, Aubry K. (Author) , Gunkel, Nikolas (Author)
Format: Article (Journal)
Language:English
Published: 23 February 2023
In: Redox Biology
Year: 2023, Volume: 62, Pages: 1-19
ISSN:2213-2317
DOI:10.1016/j.redox.2023.102639
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.redox.2023.102639
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S221323172300040X
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Author Notes:Jana Samarin, Piotr Fabrowski, Roman Kurilov, Hana Nuskova, Johanna Hummel-Eisenbeiss, Hannelore Pink, Nan Li, Vivienn Weru, Hamed Alborzinia, Umut Yildiz, Laura Grob, Minerva Taubert, Marie Czech, Michael Morgen, Christina Brandstädter, Katja Becker, Lianghao Mao, Ashok Kumar Jayavelu, Angela Goncalves, Ulrike Uhrig, Jeanette Seiler, Yanhong Lyu, Sven Diederichs, Ursula Klingmüller, Martina Muckenthaler, Annette Kopp-Schneider, Aurelio Teleman, Aubry K. Miller, Nikolas Gunkel
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Summary: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.
Item Description:Gesehen am 01.02.2024
Physical Description:Online Resource
ISSN:2213-2317
DOI:10.1016/j.redox.2023.102639

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