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Cited by 1,198

The DOI matches its Crossref record; 449 of the 449 references it cites were found in a registry or an index.

DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer

Open access
Huang, Rui-Xue, Zhou, Ping-Kun·2020·Signal Transduction and Targeted Therapy

Abstract

Radiotherapy is one of the most common countermeasures for treating a wide range of tumors. However, the radioresistance of cancer cells is still a major limitation for radiotherapy applications. Efforts are continuously ongoing to explore sensitizing targets and develop radiosensitizers for improving the outcomes of radiotherapy. DNA double-strand breaks are the most lethal lesions induced by ionizing radiation and can trigger a series of cellular DNA damage responses (DDRs), including those helping cells recover from radiation injuries, such as the activation of DNA damage sensing and early transduction pathways, cell cycle arrest, and DNA repair. Obviously, these protective DDRs confer tumor radioresistance. Targeting DDR signaling pathways has become an attractive strategy for overcoming tumor radioresistance, and some important advances and breakthroughs have already been achieved in recent years. On the basis of comprehensively reviewing the DDR signal pathways, we provide an update on the novel and promising druggable targets emerging from DDR pathways that can be exploited for radiosensitization. We further discuss recent advances identified from preclinical studies, current clinical trials, and clinical application of chemical inhibitors targeting key DDR proteins, including DNA-PKcs (DNA-dependent protein kinase, catalytic subunit), ATM/ATR (ataxia–telangiectasia mutated and Rad3-related), the MRN (MRE11-RAD50-NBS1) complex, the PARP (poly[ADP-ribose] polymerase) family, MDC1, Wee1, LIG4 (ligase IV), CDK1, BRCA1 (BRCA1 C terminal), CHK1, and HIF-1 (hypoxia-inducible factor-1). Challenges for ionizing radiation-induced signal transduction and targeted therapy are also discussed based on recent achievements in the biological field of radiotherapy.

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Metadata

Authors
Huang, R.-X., & Zhou, P.-K.
Venue
Signal Transduction and Targeted Therapy
Published
2020-05-01
Volume
5
Issue
1
Pages
60-60
ISSN
2059-3635 (ISSN-L)
OpenAlex
W3022486080
Cited by
1,198
References
449
FWCI
33.75
Type
journal article
Language
en
Open access
gold

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CoChat. (2026). Citation check: DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer. https://app.cochat.ai/papers/10.1038/s41392-020-0150-x
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Huang, R.-X., & Zhou, P.-K. (2020). DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer. Signal Transduction and Targeted Therapy. https://doi.org/10.1038/s41392-020-0150-x

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