Correlation Engine 2.0
Clear Search sequence regions


Sizes of these terms reflect their relevance to your search.

Immune checkpoint blockade (ICB) has shown immense promise for treating patients with various cancer types, but its effectiveness relies on our ability to identify likely responders. Here, we examined the association between mutations in 25 core DNA repair genes and ICB outcomes in 6619 patients across 9 cancer types with advanced disease and MSK-IMPACT tumor sequencing. Notably, we observed that mutations in 7 of the DNA repair genes (ATM, ATR, POLE, ERCC4, NBN, RAD50, PARP1) were significantly associated with improved overall survival in ICB-treated patients (p < 0.05 for all) and had significant interaction with treatment (pinteraction <0.05 for all). Similarly, DNA repair mutations were enriched in other cancer types not previously assessed and primary tumors of unknown origins, suggesting that mutations could serve as a biomarker independent of cancer type. Although our cohort was enriched in certain cancer types, such as melanoma and non-small cell lung cancer, and clinically matched samples were not assessed, our study provides a robust approach in characterizing clinically-adoptable biomarkers that can select for potential ICB responders. Copyright © 2022. Published by Elsevier Inc.

Citation

Jimmy A Guo, Mohammed Alshalalfa, Daniel Y Kim, Hannah I Hoffman, Carina Shiau, Jennifer Su, William L Hwang, Brandon A Mahal. DNA repair and immune checkpoint blockade response. Cancer genetics. 2022 Jun;264-265:1-4

Expand section icon Mesh Tags

Expand section icon Substances


PMID: 35245846

View Full Text