Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Jul;7(7):675-693.
doi: 10.1158/2159-8290.CD-17-0226. Epub 2017 Jun 19.

DNA Damage and Repair Biomarkers of Immunotherapy Response

Kent W Mouw  1   2   3 , Michael S Goldberg  2   4 , Panagiotis A Konstantinopoulos  2   5   6 , Alan D D'Andrea  7   2   3   6
Affiliations
Review

DNA Damage and Repair Biomarkers of Immunotherapy Response

Kent W Mouw et al. Cancer Discov. 2017 Jul.

Abstract

DNA-damaging agents are widely used in clinical oncology and exploit deficiencies in tumor DNA repair. Given the expanding role of immune checkpoint blockade as a therapeutic strategy, the interaction of tumor DNA damage with the immune system has recently come into focus, and it is now clear that the tumor DNA repair landscape has an important role in driving response to immune checkpoint blockade. Here, we summarize the mechanisms by which DNA damage and genomic instability have been found to shape the antitumor immune response and describe clinical efforts to use DNA repair biomarkers to guide use of immune-directed therapies.Significance: Only a subset of patients respond to immune checkpoint blockade, and reliable predictive biomarkers of response are needed to guide therapy decisions. DNA repair deficiency is common among tumors, and emerging experimental and clinical evidence suggests that features of genomic instability are associated with response to immune-directed therapies. Cancer Discov; 7(7); 675-93. ©2017 AACR.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest: P.K. has served on advisory boards for Vertex, Pfizer, and Merck.

Figures

Figure 1
Figure 1
DNA Damage Modulates Tumor Immunity
Figure 2
Figure 2
Representative Clinical Trials of ICB Agents in Combination with DNA Damaging Agents or in DNA Repair-Deficient Settings
See this image and copyright information in PMC

References

    1. Hoeijmakers JH. DNA damage, aging, and cancer. N Engl J Med. 2009;361(15):1475–85. - PubMed
    1. Roos WP, Thomas AD, Kaina B. DNA damage and the balance between survival and death in cancer biology. Nat Rev Cancer. 2016;16(1):20–33. - PubMed
    1. Burrell RA, McGranahan N, Bartek J, Swanton C. The causes and consequences of genetic heterogeneity in cancer evolution. Nature. 2013;501(7467):338–45. - PubMed
    1. Khanna A. DNA damage in cancer therapeutics: a boon or a curse? Cancer Res. 2015;75(11):2133–8. - PubMed
    1. Jeggo PA, Pearl LH, Carr AM. DNA repair, genome stability and cancer: a historical perspective. Nat Rev Cancer. 2016;16(1):35–42. - PubMed

MeSH terms