Ataxia Telangiectasia Mutated Protein Loss and Benefit From Oxaliplatin-based Chemotherapy in Colorectal Cancer.
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Authors
Sundar, R
Miranda, S
Rodrigues, DN
Chénard-Poirier, M
Dolling, D
Clarke, M
Figueiredo, I
Bertan, C
Yuan, W
Ferreira, A
Chistova, R
Boysen, G
Perez, DR
Tunariu, N
Mateo, J
Wotherspoon, A
Chau, I
Cunningham, D
Valeri, N
Carreira, S
de Bono, J
Miranda, S
Rodrigues, DN
Chénard-Poirier, M
Dolling, D
Clarke, M
Figueiredo, I
Bertan, C
Yuan, W
Ferreira, A
Chistova, R
Boysen, G
Perez, DR
Tunariu, N
Mateo, J
Wotherspoon, A
Chau, I
Cunningham, D
Valeri, N
Carreira, S
de Bono, J
Document Type
Journal Article
Date
2018-12-01
Date Accepted
2018-05-31
Abstract
BACKGROUND: Loss of ataxia telangiectasia mutated (ATM), a key protein regulating DNA repair signaling, has been suggested to increase sensitivity to DNA damaging agents. We conducted a study analyzing the loss of ATM protein expression in colorectal cancer and correlated this with clinical outcomes. MATERIALS AND METHODS: The clinical outcomes data and tumor samples from metastatic colorectal cancer patients referred to the Royal Marsden Hospital Drug Development Unit (United Kingdom) from 2012 to 2016 and providing consent for a molecular characterization study were analyzed. Immunohistochemistry (IHC) slides were assessed by a pathologist for nuclear staining intensity of ATM and semiquantitatively scored. ATM loss was defined as a nuclear H-score of ≤ 10. RESULTS: Of 223 colorectal cancer samples, ATM IHC loss was identified in 17 (8%). ATM loss was independent of the RAS and RAF mutational status. ATM loss was associated with superior overall survival after first-line oxaliplatin-based therapy (49 vs. 32 months; hazard ratio [HR], 2.52) but not with irinotecan-based therapy (24 vs. 33 months; HR, 0.72). ATM loss was not prognostic for survival from the diagnosis (50 vs. 44 months; HR, 1.43). CONCLUSION: ATM could be considered a biomarker for the development of novel DNA repair targeting agents and treatment of colorectal cancer.
Citation
Clinical colorectal cancer, 2018, 17 (4), pp. 280 - 284
Source Title
Publisher
CIG MEDIA GROUP, LP
ISSN
1533-0028
eISSN
1938-0674
Research Team
Cancer Biomarkers
Medicine (RMH Smith Cunningham)
Prostate Cancer Targeted Therapy Group
Gastrointestinal Cancer Biology and Genomics
Medicine (RMH Smith Cunningham)
Prostate Cancer Targeted Therapy Group
Gastrointestinal Cancer Biology and Genomics