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Triple kill: DDR inhibitors, radiotherapy and immunotherapy leave cancer cells with no escape: DDR inhibitors, radiotherapy and immunotherapy can kill cancer cells

Radiotherapy (RT) has been widely used in the clinical treatment of cancers, but radiotherapy resistance (RR) leads to RT failure, tumor recurrence and metastasis. Many studies have been performed on the potential mechanisms behind RR, and a strong link has been found between RR and DNA damage. RT-i...

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Autores principales: Qiu, Yuyue, Hu, Xinru, Zeng, Xiaoping, Wang, Hongmei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9828448/
https://www.ncbi.nlm.nih.gov/pubmed/36305726
http://dx.doi.org/10.3724/abbs.2022153
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author Qiu, Yuyue
Hu, Xinru
Zeng, Xiaoping
Wang, Hongmei
author_facet Qiu, Yuyue
Hu, Xinru
Zeng, Xiaoping
Wang, Hongmei
author_sort Qiu, Yuyue
collection PubMed
description Radiotherapy (RT) has been widely used in the clinical treatment of cancers, but radiotherapy resistance (RR) leads to RT failure, tumor recurrence and metastasis. Many studies have been performed on the potential mechanisms behind RR, and a strong link has been found between RR and DNA damage. RT-induced DNA damage triggers a protective mechanism called the DNA damage response (DDR). DDR consists of several aspects, including the detection of DNA damage and induction of cell cycle checkpoint, DNA repair, and eventual induction of cell death. A large number of studies have shown that DDR inhibition leads to significantly enhanced sensitivity of cancer cells to RT. DDR may be an effective target for radio- and chemo-sensitization during cancer treatment. Therefore, many inhibitors of important enzymes involved in the DDR have been developed, such as PARP inhibitors, DNA-PK inhibitors, and ATM/ATR inhibitors. In addition, DNA damage also triggers the cGAS-STING signaling pathway and the ATM/ATR (CHK)/STAT pathway to induce immune infiltration and T-cell activation. This review discusses the effects of DDR pathway dysregulation on the tumor response to RT and the strategies for targeting these pathways to increase tumor susceptibility to RT. Finally, the potential for the combination treatment of radiation, DDR inhibition, and immunotherapy is described.
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spelling pubmed-98284482023-02-10 Triple kill: DDR inhibitors, radiotherapy and immunotherapy leave cancer cells with no escape: DDR inhibitors, radiotherapy and immunotherapy can kill cancer cells Qiu, Yuyue Hu, Xinru Zeng, Xiaoping Wang, Hongmei Acta Biochim Biophys Sin (Shanghai) Research Article Radiotherapy (RT) has been widely used in the clinical treatment of cancers, but radiotherapy resistance (RR) leads to RT failure, tumor recurrence and metastasis. Many studies have been performed on the potential mechanisms behind RR, and a strong link has been found between RR and DNA damage. RT-induced DNA damage triggers a protective mechanism called the DNA damage response (DDR). DDR consists of several aspects, including the detection of DNA damage and induction of cell cycle checkpoint, DNA repair, and eventual induction of cell death. A large number of studies have shown that DDR inhibition leads to significantly enhanced sensitivity of cancer cells to RT. DDR may be an effective target for radio- and chemo-sensitization during cancer treatment. Therefore, many inhibitors of important enzymes involved in the DDR have been developed, such as PARP inhibitors, DNA-PK inhibitors, and ATM/ATR inhibitors. In addition, DNA damage also triggers the cGAS-STING signaling pathway and the ATM/ATR (CHK)/STAT pathway to induce immune infiltration and T-cell activation. This review discusses the effects of DDR pathway dysregulation on the tumor response to RT and the strategies for targeting these pathways to increase tumor susceptibility to RT. Finally, the potential for the combination treatment of radiation, DDR inhibition, and immunotherapy is described. Oxford University Press 2022-10-21 /pmc/articles/PMC9828448/ /pubmed/36305726 http://dx.doi.org/10.3724/abbs.2022153 Text en © The Author(s) 2021. 0 https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/).
spellingShingle Research Article
Qiu, Yuyue
Hu, Xinru
Zeng, Xiaoping
Wang, Hongmei
Triple kill: DDR inhibitors, radiotherapy and immunotherapy leave cancer cells with no escape: DDR inhibitors, radiotherapy and immunotherapy can kill cancer cells
title Triple kill: DDR inhibitors, radiotherapy and immunotherapy leave cancer cells with no escape: DDR inhibitors, radiotherapy and immunotherapy can kill cancer cells
title_full Triple kill: DDR inhibitors, radiotherapy and immunotherapy leave cancer cells with no escape: DDR inhibitors, radiotherapy and immunotherapy can kill cancer cells
title_fullStr Triple kill: DDR inhibitors, radiotherapy and immunotherapy leave cancer cells with no escape: DDR inhibitors, radiotherapy and immunotherapy can kill cancer cells
title_full_unstemmed Triple kill: DDR inhibitors, radiotherapy and immunotherapy leave cancer cells with no escape: DDR inhibitors, radiotherapy and immunotherapy can kill cancer cells
title_short Triple kill: DDR inhibitors, radiotherapy and immunotherapy leave cancer cells with no escape: DDR inhibitors, radiotherapy and immunotherapy can kill cancer cells
title_sort triple kill: ddr inhibitors, radiotherapy and immunotherapy leave cancer cells with no escape: ddr inhibitors, radiotherapy and immunotherapy can kill cancer cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9828448/
https://www.ncbi.nlm.nih.gov/pubmed/36305726
http://dx.doi.org/10.3724/abbs.2022153
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