Crosstalk between immune checkpoint and DNA damage response inhibitors for radiosensitization of tumors

Purpose This review article is intended to provide a perspective overview of potential strategies to overcome radiation resistance of tumors through the combined use of immune checkpoint and DNA repair inhibitors. Methods A literature search was conducted in PubMed using the terms (“DNA repair* and...

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Published inStrahlentherapie und Onkologie Vol. 199; no. 12; pp. 1152 - 1163
Main Authors Classen, Sandra, Petersen, Cordula, Borgmann, Kerstin
Format Journal Article
LanguageEnglish
Published Berlin/Heidelberg Springer Berlin Heidelberg 01.12.2023
Springer Nature B.V
Subjects
Cell death
DNA damage
DNA repair
Immune system
Inhibitors
Medicine
Medicine & Public Health
Oncology
Radiation
Radiation damage
Radiation therapy
Radiation tolerance
Radiotherapy
Review Article
Tumors
cGAS/STING activation
DNA damage response
DNA repair
Cytosolic dsDNA
PARP inhibition
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Abstract Purpose This review article is intended to provide a perspective overview of potential strategies to overcome radiation resistance of tumors through the combined use of immune checkpoint and DNA repair inhibitors. Methods A literature search was conducted in PubMed using the terms (“DNA repair* and DNA damage response* and intracellular immune response* and immune checkpoint inhibition* and radio*”) until January 31, 2023. Articles were manually selected based on their relevance to the topics analyzed. Results Modern radiotherapy offers a wide range of options for tumor treatment. Radiation-resistant subpopulations of the tumor pose a particular challenge for complete cure. This is due to the enhanced activation of molecular defense mechanisms that prevent cell death because of DNA damage. Novel approaches to enhance tumor cure are provided by immune checkpoint inhibitors, but their effectiveness, especially in tumors without increased mutational burden, also remains limited. Combining inhibitors of both immune checkpoints and DNA damage response with radiation may be an attractive option to augment existing therapies and is the subject of the data summarized here. Conclusion The combination of tested inhibitors of DNA damage and immune responses in preclinical models opens additional attractive options for the radiosensitization of tumors and represents a promising application for future therapeutic approaches.
AbstractList This review article is intended to provide a perspective overview of potential strategies to overcome radiation resistance of tumors through the combined use of immune checkpoint and DNA repair inhibitors. A literature search was conducted in PubMed using the terms ("DNA repair* and DNA damage response* and intracellular immune response* and immune checkpoint inhibition* and radio*") until January 31, 2023. Articles were manually selected based on their relevance to the topics analyzed. Modern radiotherapy offers a wide range of options for tumor treatment. Radiation-resistant subpopulations of the tumor pose a particular challenge for complete cure. This is due to the enhanced activation of molecular defense mechanisms that prevent cell death because of DNA damage. Novel approaches to enhance tumor cure are provided by immune checkpoint inhibitors, but their effectiveness, especially in tumors without increased mutational burden, also remains limited. Combining inhibitors of both immune checkpoints and DNA damage response with radiation may be an attractive option to augment existing therapies and is the subject of the data summarized here. The combination of tested inhibitors of DNA damage and immune responses in preclinical models opens additional attractive options for the radiosensitization of tumors and represents a promising application for future therapeutic approaches.
PurposeThis review article is intended to provide a perspective overview of potential strategies to overcome radiation resistance of tumors through the combined use of immune checkpoint and DNA repair inhibitors.MethodsA literature search was conducted in PubMed using the terms (“DNA repair* and DNA damage response* and intracellular immune response* and immune checkpoint inhibition* and radio*”) until January 31, 2023. Articles were manually selected based on their relevance to the topics analyzed.ResultsModern radiotherapy offers a wide range of options for tumor treatment. Radiation-resistant subpopulations of the tumor pose a particular challenge for complete cure. This is due to the enhanced activation of molecular defense mechanisms that prevent cell death because of DNA damage. Novel approaches to enhance tumor cure are provided by immune checkpoint inhibitors, but their effectiveness, especially in tumors without increased mutational burden, also remains limited. Combining inhibitors of both immune checkpoints and DNA damage response with radiation may be an attractive option to augment existing therapies and is the subject of the data summarized here.ConclusionThe combination of tested inhibitors of DNA damage and immune responses in preclinical models opens additional attractive options for the radiosensitization of tumors and represents a promising application for future therapeutic approaches.
Purpose This review article is intended to provide a perspective overview of potential strategies to overcome radiation resistance of tumors through the combined use of immune checkpoint and DNA repair inhibitors. Methods A literature search was conducted in PubMed using the terms (“DNA repair* and DNA damage response* and intracellular immune response* and immune checkpoint inhibition* and radio*”) until January 31, 2023. Articles were manually selected based on their relevance to the topics analyzed. Results Modern radiotherapy offers a wide range of options for tumor treatment. Radiation-resistant subpopulations of the tumor pose a particular challenge for complete cure. This is due to the enhanced activation of molecular defense mechanisms that prevent cell death because of DNA damage. Novel approaches to enhance tumor cure are provided by immune checkpoint inhibitors, but their effectiveness, especially in tumors without increased mutational burden, also remains limited. Combining inhibitors of both immune checkpoints and DNA damage response with radiation may be an attractive option to augment existing therapies and is the subject of the data summarized here. Conclusion The combination of tested inhibitors of DNA damage and immune responses in preclinical models opens additional attractive options for the radiosensitization of tumors and represents a promising application for future therapeutic approaches.
This review article is intended to provide a perspective overview of potential strategies to overcome radiation resistance of tumors through the combined use of immune checkpoint and DNA repair inhibitors.PURPOSEThis review article is intended to provide a perspective overview of potential strategies to overcome radiation resistance of tumors through the combined use of immune checkpoint and DNA repair inhibitors.A literature search was conducted in PubMed using the terms ("DNA repair* and DNA damage response* and intracellular immune response* and immune checkpoint inhibition* and radio*") until January 31, 2023. Articles were manually selected based on their relevance to the topics analyzed.METHODSA literature search was conducted in PubMed using the terms ("DNA repair* and DNA damage response* and intracellular immune response* and immune checkpoint inhibition* and radio*") until January 31, 2023. Articles were manually selected based on their relevance to the topics analyzed.Modern radiotherapy offers a wide range of options for tumor treatment. Radiation-resistant subpopulations of the tumor pose a particular challenge for complete cure. This is due to the enhanced activation of molecular defense mechanisms that prevent cell death because of DNA damage. Novel approaches to enhance tumor cure are provided by immune checkpoint inhibitors, but their effectiveness, especially in tumors without increased mutational burden, also remains limited. Combining inhibitors of both immune checkpoints and DNA damage response with radiation may be an attractive option to augment existing therapies and is the subject of the data summarized here.RESULTSModern radiotherapy offers a wide range of options for tumor treatment. Radiation-resistant subpopulations of the tumor pose a particular challenge for complete cure. This is due to the enhanced activation of molecular defense mechanisms that prevent cell death because of DNA damage. Novel approaches to enhance tumor cure are provided by immune checkpoint inhibitors, but their effectiveness, especially in tumors without increased mutational burden, also remains limited. Combining inhibitors of both immune checkpoints and DNA damage response with radiation may be an attractive option to augment existing therapies and is the subject of the data summarized here.The combination of tested inhibitors of DNA damage and immune responses in preclinical models opens additional attractive options for the radiosensitization of tumors and represents a promising application for future therapeutic approaches.CONCLUSIONThe combination of tested inhibitors of DNA damage and immune responses in preclinical models opens additional attractive options for the radiosensitization of tumors and represents a promising application for future therapeutic approaches.
Author Classen, Sandra
Borgmann, Kerstin
Petersen, Cordula
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  surname: Borgmann
  fullname: Borgmann, Kerstin
  email: borgmann@uke.de
  organization: Laboratory of Radiobiology and Radiation Oncology, Department of Radiotherapy and Radiation Oncology, Center of Oncology, University Medical Center Hamburg-Eppendorf
BackLink https://www.ncbi.nlm.nih.gov/pubmed/37420037$$D View this record in MEDLINE/PubMed
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Keywords cGAS/STING activation
DNA damage response
DNA repair
Cytosolic dsDNA
PARP inhibition
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Snippet Purpose This review article is intended to provide a perspective overview of potential strategies to overcome radiation resistance of tumors through the...
This review article is intended to provide a perspective overview of potential strategies to overcome radiation resistance of tumors through the combined use...
PurposeThis review article is intended to provide a perspective overview of potential strategies to overcome radiation resistance of tumors through the...
This review article is intended to provide a perspective overview of potential strategies to overcome radiation resistance of tumors through the combined use...
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SubjectTerms Cell death
DNA damage
DNA repair
Immune system
Inhibitors
Medicine
Medicine & Public Health
Oncology
Radiation
Radiation damage
Radiation therapy
Radiation tolerance
Radiotherapy
Review Article
Tumors
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Title Crosstalk between immune checkpoint and DNA damage response inhibitors for radiosensitization of tumors
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