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The role of APOBEC3B in lung tumor evolution and targeted cancer therapy resistance
Nature genetics, 2024-01, Vol.56 (1), p.60-73
2024

Details

Autor(en) / Beteiligte
Titel
The role of APOBEC3B in lung tumor evolution and targeted cancer therapy resistance
Ist Teil von
  • Nature genetics, 2024-01, Vol.56 (1), p.60-73
Ort / Verlag
United States: Nature Publishing Group
Erscheinungsjahr
2024
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
  • 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.
Sprache
Englisch
Identifikatoren
ISSN: 1061-4036
eISSN: 1546-1718
DOI: 10.1038/s41588-023-01592-8
Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10786726
Format
–
Schlagworte
Animal models, Animals, Apolipoprotein B, Apolipoproteins, Cancer therapies, Carcinoma, Non-Small-Cell Lung - drug therapy, Carcinoma, Non-Small-Cell Lung - genetics, Cell death, Chromosomes, Cytidine Deaminase - genetics, Datasets, Enzymes, Epidermal growth factor, Epidermal growth factor receptors, ErbB Receptors - genetics, ErbB Receptors - metabolism, Genomes, Growth factors, Humans, Kinases, Lung cancer, Lung Neoplasms - drug therapy, Lung Neoplasms - genetics, Mice, Minor Histocompatibility Antigens - genetics, Minor Histocompatibility Antigens - metabolism, mRNA, Mutation, NF-κB protein, Non-small cell lung carcinoma, RNA editing, Small cell lung carcinoma, Targeted cancer therapy, Therapy, Transgenic animals, Tumorigenesis, Tumors, Up-regulation, Up-Regulation - genetics

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