Low level of antioxidant capacity biomarkers but not target overexpression predicts vulnerability to ROS-inducing drugs
Abstract 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: |
Preprint |
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Erscheinungsjahr: |
2023 |
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Erschienen: |
2023 |
Enthalten in: |
bioRxiv.org - (2023) vom: 21. Jan. Zur Gesamtaufnahme - year:2023 |
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Sprache: |
Englisch |
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Beteiligte Personen: |
Samarin, Jana [VerfasserIn] |
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Links: |
Volltext [kostenfrei] |
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Themen: |
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doi: |
10.1101/2023.01.17.524372 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
XBI038461889 |
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520 | |a Abstract 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 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 | |
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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 | |
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700 | 1 | |a Gunkel, Nikolas |e verfasserin |4 aut | |
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