The role of APOBEC3B in lung tumor evolution and targeted cancer therapy resistance Journal Article

   


Authors: Caswell, D. R.; Gui, P.; Mayekar, M. K.; Law, E. K.; Pich, O.; Bailey, C.; Boumelha, J.; Kerr, D. L.; Blakely, C. M.; Manabe, T.; Martinez-Ruiz, C.; Bakker, B.; De Dios Palomino Villcas, J.; I. Vokes, N.; Dietzen, M.; Angelova, M.; Gini, B.; Tamaki, W.; Allegakoen, P.; Wu, W.; Humpton, T. J.; Hill, W.; Tomaschko, M.; Lu, W. T.; Haderk, F.; Al Bakir, M.; Nagano, A.; Gimeno-Valiente, F.; de Carné Trécesson, S.; Vendramin, R.; Barbè, V.; Mugabo, M.; Weeden, C. E.; Rowan, A.; McCoach, C. E.; Almeida, B.; Green, M.; Gomez, C.; Nanjo, S.; Barbosa, D.; Moore, C.; Przewrocka, J.; Black, J. R. M.; Grönroos, E.; Suarez-Bonnet, A.; Priestnall, S. L.; Zverev, C.; Lighterness, S.; Cormack, J.; Olivas, V.; Cech, L.; Andrews, T.; Rule, B.; Jiao, Y.; Zhang, X.; Ashford, P.; Durfee, C.; Venkatesan, S.; Temiz, N. A.; Tan, L.; Larson, L. K.; Argyris, P. P.; Brown, W. L.; Yu, E. A.; Rotow, J. K.; Guha, U.; Roper, N.; Yu, J.; Vogel, R. I.; Thomas, N. J.; Marra, A.; Selenica, P.; Yu, H.; Bakhoum, S. F.; Chew, S. K.; Reis-Filho, J. S.; Jamal-Hanjani, M.; Vousden, K. H.; McGranahan, N.; Van Allen, E. M.; Kanu, N.; Harris, R. S.; Downward, J.; Bivona, T. G.; Swanton, C.
Article Title: The role of APOBEC3B in lung tumor evolution and targeted cancer therapy resistance
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. © 2023, The Author(s).
Keywords: genetics; mutation; mouse; animal; metabolism; animals; mice; carcinoma, non-small-cell lung; lung neoplasms; epidermal growth factor receptor; lung tumor; cytidine deaminase; upregulation; up-regulation; non small cell lung cancer; minor histocompatibility antigens; minor histocompatibility antigen; erbb receptors; humans; human; apobec3b protein, human
Journal Title: Nature Genetics
Volume: 56
Issue: 1
ISSN: 1061-4036
Publisher: Nature Publishing Group  
Date Published: 2024-01-01
Start Page: 60
End Page: 73
Language: English
DOI: 10.1038/s41588-023-01592-8
PUBMED: 38049664
PROVIDER: scopus
PMCID: PMC10786726
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85178453054&doi=10.1038%2fs41588-023-01592-8&partnerID=40&md5=cd6502e431325b5cd6f3c257537bcd6a
Notes: Article -- Source: Scopus
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MSK Authors
  1. Helena Alexandra Yu
    281 Yu
  2. Jorge Sergio Reis-Filho
    639 Reis-Filho
  3. Samuel F Bakhoum
    81 Bakhoum
  4. Pier Selenica
    189 Selenica
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