Low level of antioxidant capacity biomarkers but not target overexpression predicts vulnerability to ROS-inducing drugs
Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:62 |
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| Enthalten in: |
Redox biology - 62(2023) vom: 15. Juni, Seite 102639 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Samarin, Jana [VerfasserIn] |
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| Links: |
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| Themen: |
Antioxidants |
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| Anmerkungen: |
Date Completed 12.05.2023 Date Revised 10.06.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.redox.2023.102639 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a 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 | ||
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| 700 | 1 | |a Fabrowski, Piotr |e verfasserin |4 aut | |
| 700 | 1 | |a Kurilov, Roman |e verfasserin |4 aut | |
| 700 | 1 | |a Nuskova, Hana |e verfasserin |4 aut | |
| 700 | 1 | |a Hummel-Eisenbeiss, Johanna |e verfasserin |4 aut | |
| 700 | 1 | |a Pink, Hannelore |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Nan |e verfasserin |4 aut | |
| 700 | 1 | |a Weru, Vivienn |e verfasserin |4 aut | |
| 700 | 1 | |a Alborzinia, Hamed |e verfasserin |4 aut | |
| 700 | 1 | |a Yildiz, Umut |e verfasserin |4 aut | |
| 700 | 1 | |a Grob, Laura |e verfasserin |4 aut | |
| 700 | 1 | |a Taubert, Minerva |e verfasserin |4 aut | |
| 700 | 1 | |a Czech, Marie |e verfasserin |4 aut | |
| 700 | 1 | |a Morgen, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Brandstädter, Christina |e verfasserin |4 aut | |
| 700 | 1 | |a Becker, Katja |e verfasserin |4 aut | |
| 700 | 1 | |a Mao, Lianghao |e verfasserin |4 aut | |
| 700 | 1 | |a Jayavelu, Ashok Kumar |e verfasserin |4 aut | |
| 700 | 1 | |a Goncalves, Angela |e verfasserin |4 aut | |
| 700 | 1 | |a Uhrig, Ulrike |e verfasserin |4 aut | |
| 700 | 1 | |a Seiler, Jeanette |e verfasserin |4 aut | |
| 700 | 1 | |a Lyu, Yanhong |e verfasserin |4 aut | |
| 700 | 1 | |a Diederichs, Sven |e verfasserin |4 aut | |
| 700 | 1 | |a Klingmüller, Ursula |e verfasserin |4 aut | |
| 700 | 1 | |a Muckenthaler, Martina |e verfasserin |4 aut | |
| 700 | 1 | |a Kopp-Schneider, Annette |e verfasserin |4 aut | |
| 700 | 1 | |a Teleman, Aurelio |e verfasserin |4 aut | |
| 700 | 1 | |a Miller, Aubry K |e verfasserin |4 aut | |
| 700 | 1 | |a Gunkel, Nikolas |e verfasserin |4 aut | |
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