TY  - JOUR
AU  - Samarin, Jana
AU  - Fabrowski, Piotr
AU  - Kurilov, Roman
AU  - Nuskova, Hana
AU  - Hummel-Eisenbeiss, Johanna
AU  - Pink, Hannelore
AU  - Li, Nan
AU  - Weru, Vivienn
AU  - Alborzinia, Hamed
AU  - Yildiz, Umut
AU  - Grob, Laura
AU  - Täubert, Minerva Jazmin
AU  - Czech, Marie
AU  - Morgen, Michael
AU  - Brandstädter, Christina
AU  - Becker, Katja
AU  - Mao, Lianghao
AU  - Jayavelu, Ashok Kumar
AU  - Goncalves, Angela
AU  - Uhrig, Ulrike
AU  - Seiler, Jeanette Simone
AU  - Lyu, Yanhong
AU  - Diederichs, Sven
AU  - Klingmüller, Ursula
AU  - Muckenthaler, Martina
AU  - Kopp-Schneider, Annette
AU  - Teleman, Aurelio
AU  - Miller, Aubry
AU  - Gunkel, Peter Nikolas
TI  - Low level of antioxidant capacity biomarkers but not target overexpression predicts vulnerability to ROS-inducing drugs.
JO  - Redox Biology
VL  - 62
SN  - 2213-2317
CY  - Amsterdam [u.a.]
PB  - Elsevier
M1  - DKFZ-2023-00591
SP  - 102639
PY  - 2023
N1  - #EA:A390#LA:A390#
AB  - 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.
KW  - Biomarker (Other)
KW  - Ferroptosis (Other)
KW  - NRF2 (Other)
KW  - Nitric oxide (Other)
KW  - TXNRD1 inhibitor (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:36958250
DO  - DOI:10.1016/j.redox.2023.102639
UR  - https://inrepo02.dkfz.de/record/274427
ER  -