DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer
By Rui-Xue Huang, Pingkun Zhou. Signal Transduction and Targeted Therapy, 2020
1,000 citations recorded by the source corpus.
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.
Subfields: Molecular Biology, Oncology
View Paper: https://www.semanticscholar.org/paper/4b6015780f94488789e16e20e4eb548d66de1867
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In Molecular Biology
Citations in the corpus
- The Chemistry of Reactive Oxygen Species (ROS) Revisited: Outlining Their Role in Biological Macromolecules (DNA, Lipids and Proteins) and Induced Pathologies (2021, background): “A network of events known as the DNA damage response (DDR) is triggered in response to DNA damage [30].”
- DNA damage repair: historical perspectives, mechanistic pathways and clinical translation for targeted cancer therapy (2021, background): “We focused on the critical issue of recognizing and identifying DNA damage signals to activate the subsequent biological response cascade.(6) Therefore, in this review, we focus on the association between DDR and cancer.”