The DNA damage response in immunotherapy and radiation

Purpose: Deficiencies in DNA damage repair (DDR) and response represent a common alteration in tumors, and exploitation of this feature using therapeutics has become more prominent. Methods and materials: Recent work has highlighted the important interaction between DDR defects, as well as DDR targe...

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Main Authors: Robert M. Samstein, MD, PhD, Nadeem Riaz, MD
Format: Article
Language:English
Published: Elsevier 2018-10-01
Series:Advances in Radiation Oncology
Online Access:http://www.sciencedirect.com/science/article/pii/S2452109418301490
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author Robert M. Samstein, MD, PhD
Nadeem Riaz, MD
author_facet Robert M. Samstein, MD, PhD
Nadeem Riaz, MD
author_sort Robert M. Samstein, MD, PhD
collection DOAJ
description Purpose: Deficiencies in DNA damage repair (DDR) and response represent a common alteration in tumors, and exploitation of this feature using therapeutics has become more prominent. Methods and materials: Recent work has highlighted the important interaction between DDR defects, as well as DDR targeting agents such as radiation and the immunogenicity of the tumor. This relationship emphasizes the potential for combination therapeutics with immune checkpoint inhibitors (ICI). Somatic mutations and DDR defects are some of the strongest predictors of response to ICI. Results: This review highlights the interplay among DDR pathways, ionizing radiation, and ICI efficacy. The mechanisms of radiation immunogenicity, including the cytosolic DNA sensing cGAS/STING pathways, are also described. Conclusions: A greater mechanistic understanding of the complex interaction between the DNA damage response and the immune system will expand the therapeutic potential of immunotherapy for patients with advanced cancer.
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spelling doaj.art-f66901c5a88f49abab79c3189ddeb7ba2022-12-22T00:13:45ZengElsevierAdvances in Radiation Oncology2452-10942018-10-0134527533The DNA damage response in immunotherapy and radiationRobert M. Samstein, MD, PhD0Nadeem Riaz, MD1Corresponding author. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065.; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New YorkDepartment of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New YorkPurpose: Deficiencies in DNA damage repair (DDR) and response represent a common alteration in tumors, and exploitation of this feature using therapeutics has become more prominent. Methods and materials: Recent work has highlighted the important interaction between DDR defects, as well as DDR targeting agents such as radiation and the immunogenicity of the tumor. This relationship emphasizes the potential for combination therapeutics with immune checkpoint inhibitors (ICI). Somatic mutations and DDR defects are some of the strongest predictors of response to ICI. Results: This review highlights the interplay among DDR pathways, ionizing radiation, and ICI efficacy. The mechanisms of radiation immunogenicity, including the cytosolic DNA sensing cGAS/STING pathways, are also described. Conclusions: A greater mechanistic understanding of the complex interaction between the DNA damage response and the immune system will expand the therapeutic potential of immunotherapy for patients with advanced cancer.http://www.sciencedirect.com/science/article/pii/S2452109418301490
spellingShingle Robert M. Samstein, MD, PhD
Nadeem Riaz, MD
The DNA damage response in immunotherapy and radiation
Advances in Radiation Oncology
title The DNA damage response in immunotherapy and radiation
title_full The DNA damage response in immunotherapy and radiation
title_fullStr The DNA damage response in immunotherapy and radiation
title_full_unstemmed The DNA damage response in immunotherapy and radiation
title_short The DNA damage response in immunotherapy and radiation
title_sort dna damage response in immunotherapy and radiation
url http://www.sciencedirect.com/science/article/pii/S2452109418301490
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