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Biological insights in non-small cell lung cancer

Cancer Biology & Medicine 2023年第7期20卷 500-518页

作者： Rafael Rosell Anisha jain Jordi Codony-Servat Eloisa Jantus-Lewintre Blake Morrison Jordi Barretina Ginesta maría González-Cao Germans Trias i Pujol Research Institute Badalona 08028Spain IOR Hospital Quiron-DexeusBarcelona 08028Spain Department of Microbiology JSS Academy of Higher Education&ResearchMysuru 570015India Pangaea Oncology Hospital Quiron-DexeusBarcelona 08028Spain Department of Biotechnology Universitat Politècnica de ValenciaMixed Unit TRIAL(General University Hospital of Valencia Research Foundation and Príncipe Felipe Research Center)CIBERONCValencia 46014Spain Sumitomo Pharma Oncology Inc.CambridgeMA and LehiUT 84043USA

Lung oncogenesis relies on intracellular cysteine to overcome oxidative *** tumor types,including non-small cell lung cancer(NSCLC),upregulate the system x-c cystine/glutamate antiporter(xCT)through overexpression of the cystine transporter SLC7A11,thus sustaining intracellular cysteine levels to support glutathione *** factor erythroid 2-related factor 2(NRF2)serves as a master regulator of oxidative stress resistance by regulating SLC7A11,whereas kelch-like ECH-associated protein(kEAP1)acts as a cytoplasmic repressor of the oxidative responsive transcription factor *** in kEAP1/NRF2 and p53 induce SLC7A11 activation in *** cystine is crucial in supplying the intracellular cysteine levels necessary to combat oxidative *** in cystine availability lead to iron-dependent lipid peroxidation,thus resulting in a type of cell death called *** inhibitors of xCT(either SLC7A11 or GPX4)induce ferroptosis of NSCLC cells and other tumor *** cystine uptake is impaired,the intracellular cysteine pool can be sustained by the transsulfuration pathway,which is catalyzed by cystathionine-B-synthase(CBS)and cystathionine g-lyase(CSE).The involvement of exogenous cysteine/cystine and the transsulfuration pathway in the cysteine pool and downstream metabolites results in compromised CD8^(+)T cell function and evasion of immunotherapy,diminishing immune response and potentially reducing the effectiveness of immunotherapeutic *** is a previously unrecognized form of regulated cell *** NSCLCs driven by EGFR,ALk,or kRAS,selective inhibitors induce pyroptotic cell death as well as *** targeted therapy,the mitochondrial intrinsic apoptotic pathway is activated,thus leading to the cleavage and activation of ***,gasdermin E is activated,thus leading to permeabilization of the cytoplasmic membrane and cell-lytic pyroptosis(indicated by characte

关键词： Solute carrier family 7 member 11(SLC7A11) nuclear factor erythroid 2-related factor 2(NRF2) ferroptosis pyroptosis kRAS G12C allele-specific inhibitors non-small cell lung cancer(NSCLC)

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