PMID- 32355263
OWN - NLM
STAT- MEDLINE
DCOM- 20211006
LR  - 20211006
IS  - 2059-3635 (Electronic)
IS  - 2095-9907 (Print)
IS  - 2059-3635 (Linking)
VI  - 5
IP  - 1
DP  - 2020 May 1
TI  - DNA damage response signaling pathways and targets for radiotherapy sensitization 
      in cancer.
PG  - 60
LID - 10.1038/s41392-020-0150-x [doi]
LID - 60
AB  - 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.
FAU - Huang, Rui-Xue
AU  - Huang RX
AD  - Department of Occupational and Environmental Health, Xiangya School of Public 
      Health, Central South University, 410078, Changsha, People's Republic of China.
FAU - Zhou, Ping-Kun
AU  - Zhou PK
AUID- ORCID: 0000-0001-7666-1209
AD  - Department of Radiation Biology, Beijing Key Laboratory for Radiobiology, Beijing 
      Institute of Radiation Medicine, AMMS, 100850, Beijing, People's Republic of 
      China. zhoupk@bmi.ac.cn.
AD  - Institute for Chemical Carcinogenesis, State Key Laboratory of Respiratory, 
      Guangzhou Medical University, 511436, Guangzhou, People's Republic of China. 
      zhoupk@bmi.ac.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20200501
PL  - England
TA  - Signal Transduct Target Ther
JT  - Signal transduction and targeted therapy
JID - 101676423
RN  - 0 (Neoplasm Proteins)
SB  - IM
MH  - Cell Cycle Checkpoints/*radiation effects
MH  - DNA Breaks, Double-Stranded/*radiation effects
MH  - DNA Repair/*radiation effects
MH  - Humans
MH  - Neoplasm Proteins/*metabolism
MH  - *Neoplasms/metabolism/pathology/radiotherapy
MH  - *Radiation Tolerance
MH  - Radiotherapy
MH  - Signal Transduction/*radiation effects
PMC - PMC7192953
COIS- The authors declare that they have no conflict of interest.
EDAT- 2020/05/02 06:00
MHDA- 2021/10/07 06:00
PMCR- 2020/05/01
CRDT- 2020/05/02 06:00
PHST- 2020/01/24 00:00 [received]
PHST- 2020/03/16 00:00 [accepted]
PHST- 2020/02/20 00:00 [revised]
PHST- 2020/05/02 06:00 [entrez]
PHST- 2020/05/02 06:00 [pubmed]
PHST- 2021/10/07 06:00 [medline]
PHST- 2020/05/01 00:00 [pmc-release]
AID - 10.1038/s41392-020-0150-x [pii]
AID - 150 [pii]
AID - 10.1038/s41392-020-0150-x [doi]
PST - epublish
SO  - Signal Transduct Target Ther. 2020 May 1;5(1):60. doi: 10.1038/s41392-020-0150-x.