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The role of APOBEC3B in lung tumor evolution and targeted cancer therapy resistance.
Caswell, Deborah R; Gui, Philippe; Mayekar, Manasi K; Law, Emily K; Pich, Oriol; Bailey, Chris; Boumelha, Jesse; Kerr, D Lucas; Blakely, Collin M; Manabe, Tadashi; Martinez-Ruiz, Carlos; Bakker, Bjorn; De Dios Palomino Villcas, Juan; I Vokes, Natalie; Dietzen, Michelle; Angelova, Mihaela; Gini, Beatrice; Tamaki, Whitney; Allegakoen, Paul; Wu, Wei; Humpton, Timothy J; Hill, William; Tomaschko, Mona; Lu, Wei-Ting; Haderk, Franziska; Al Bakir, Maise; Nagano, Ai; Gimeno-Valiente, Francisco; de Carné Trécesson, Sophie; Vendramin, Roberto; Barbè, Vittorio; Mugabo, Miriam; Weeden, Clare E; Rowan, Andrew; McCoach, Caroline E; Almeida, Bruna; Green, Mary; Gomez, Carlos; Nanjo, Shigeki; Barbosa, Dora; Moore, Chris; Przewrocka, Joanna; Black, James R M; Grönroos, Eva; Suarez-Bonnet, Alejandro; Priestnall, Simon L; Zverev, Caroline; Lighterness, Scott; Cormack, James; Olivas, Victor.
Afiliação
  • Caswell DR; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK. deborah.caswell@crick.ac.uk.
  • Gui P; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Mayekar MK; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Law EK; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA.
  • Pich O; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Bailey C; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Boumelha J; Oncogene Biology Laboratory, The Francis Crick Institute, London, UK.
  • Kerr DL; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Blakely CM; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Manabe T; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Martinez-Ruiz C; Cancer Genome Evolution Research Group, University College London, Cancer Institute, London, UK.
  • Bakker B; Cancer Research UK Lung Cancer Centre of Excellence, UCL Cancer Institute, London, UK.
  • De Dios Palomino Villcas J; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • I Vokes N; Core Research Laboratory, ISPRO, Florence, Italy.
  • Dietzen M; Department of Thoracic and Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Angelova M; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Gini B; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Tamaki W; Cancer Genome Evolution Research Group, University College London, Cancer Institute, London, UK.
  • Allegakoen P; Cancer Research UK Lung Cancer Centre of Excellence, UCL Cancer Institute, London, UK.
  • Wu W; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Humpton TJ; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Hill W; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Tomaschko M; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Lu WT; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Haderk F; p53 and Metabolism Laboratory, The Francis Crick Institute, London, UK.
  • Al Bakir M; CRUK Beatson Institute, Glasgow, UK.
  • Nagano A; Glasgow Caledonian University, Glasgow, UK.
  • Gimeno-Valiente F; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • de Carné Trécesson S; Oncogene Biology Laboratory, The Francis Crick Institute, London, UK.
  • Vendramin R; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Barbè V; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Mugabo M; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Weeden CE; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Rowan A; Cancer Research UK Lung Cancer Centre of Excellence, UCL Cancer Institute, London, UK.
  • McCoach CE; Oncogene Biology Laboratory, The Francis Crick Institute, London, UK.
  • Almeida B; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Green M; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Gomez C; Cancer Research UK Lung Cancer Centre of Excellence, UCL Cancer Institute, London, UK.
  • Nanjo S; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Barbosa D; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Moore C; Genentech Inc, South San Francisco, CA, USA.
  • Przewrocka J; The Roger Williams Institute of Hepatology, Foundation for Liver Research, London, UK.
  • Black JRM; Faculty of Life Sciences & Medicine, King's College London, London, UK.
  • Grönroos E; Experimental Histopathology, The Francis Crick Institute, London, UK.
  • Suarez-Bonnet A; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Priestnall SL; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Zverev C; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Lighterness S; Oncogene Biology Laboratory, The Francis Crick Institute, London, UK.
  • Cormack J; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Olivas V; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
Nat Genet ; 56(1): 60-73, 2024 Jan.
Article em En | MEDLINE | ID: mdl-38049664
ABSTRACT
In this study, the impact of the apolipoprotein B mRNA-editing catalytic subunit-like (APOBEC) enzyme APOBEC3B (A3B) on epidermal growth factor receptor (EGFR)-driven lung cancer was assessed. A3B expression in EGFR mutant (EGFRmut) non-small-cell lung cancer (NSCLC) mouse models constrained tumorigenesis, while A3B expression in tumors treated with EGFR-targeted cancer therapy was associated with treatment resistance. Analyses of human NSCLC models treated with EGFR-targeted therapy showed upregulation of A3B and revealed therapy-induced activation of nuclear factor kappa B (NF-κB) as an inducer of A3B expression. Significantly reduced viability was observed with A3B deficiency, and A3B was required for the enrichment of APOBEC mutation signatures, in targeted therapy-treated human NSCLC preclinical models. Upregulation of A3B was confirmed in patients with NSCLC treated with EGFR-targeted therapy. This study uncovers the multifaceted roles of A3B in NSCLC and identifies A3B as a potential target for more durable responses to targeted cancer therapy.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Pulmonar de Células não Pequenas / Neoplasias Pulmonares Limite: Animals / Humans Idioma: En Revista: Nat Genet Ano de publicação: 2024 Tipo de documento: Article
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Pulmonar de Células não Pequenas / Neoplasias Pulmonares Limite: Animals / Humans Idioma: En Revista: Nat Genet Ano de publicação: 2024 Tipo de documento: Article