The role of APOBEC3B in lung tumor evolution and targeted cancer therapy resistance.
Date
2024-01-01ICR Author
Author
Caswell, DR
Gui, P
Mayekar, MK
Law, EK
Pich, O
Bailey, C
Boumelha, J
Kerr, DL
Blakely, CM
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, TJ
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, CE
Rowan, A
McCoach, CE
Almeida, B
Green, M
Gomez, C
Nanjo, S
Barbosa, D
Moore, C
Przewrocka, J
Black, JRM
Grönroos, E
Suarez-Bonnet, A
Priestnall, SL
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, NA
Tan, L
Larson, LK
Argyris, PP
Brown, WL
Yu, EA
Rotow, JK
Guha, U
Roper, N
Yu, J
Vogel, RI
Thomas, NJ
Marra, A
Selenica, P
Yu, H
Bakhoum, SF
Chew, SK
Reis-Filho, JS
Jamal-Hanjani, M
Vousden, KH
McGranahan, N
Van Allen, EM
Kanu, N
Harris, RS
Downward, J
Bivona, TG
Swanton, C
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Humans
Animals
Mice
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Mutation
Up-Regulation
ErbB Receptors
Cytidine Deaminase
Minor Histocompatibility Antigens
Research team
Lung Cancer Group
Language
eng
Date accepted
2023-10-25
License start date
2024-01-01
Citation
Nature Genetics, 2024, 56 (1), pp. 60 - 73
Publisher
NATURE PORTFOLIO