Journal
MOLECULAR CANCER RESEARCH
Volume 19, Issue 11, Pages 1889-1899Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1541-7786.MCR-21-0301
Keywords
-
Categories
Funding
- National Natural Science Foundation of China [81903256, 81872548, 81673105, 31971167]
- China Postdoctoral Science Foundation [2018M643123]
Ask authors/readers for more resources
NHEJ, the predominant pathway for DNA repair, needs inhibitors to enhance the efficacy of radiotherapy and chemotherapy. Through screening, omipalisib was identified as an effective sensitizer for cell death induced by DNA damage, suppressing the NHEJ pathway.
As the predominant pathway for the repair of DNA double-strand breaks (DSB), non-homologous end joining (NHEJ) attenuates the efficacy of cancer treatment which relies on the introduction of DSBs, such as radiotherapy and genotoxic drugs. Identifying novel NHEJ inhibitors is of great importance for improving the therapeutic efficiency of radio- or chemotherapy. Here we miniaturized our recently developed NHEJ detecting system into a 96-well plate-based format and interrogated an FDA approved drug library containing 1732 compounds. A collection of novel hits were considered to be potential DSB repair inhibitors at the noncytotoxic concentration. We identified omipalisib as an efficient sensitizer for DNA damage-induced cell death in vitro. Furthermore, in vitro analysis uncovered the repressive effect of omipalisib on the phosphorylation of DNA-dependent protein kinase catalytic subunit induced by ionizing radiation and doxorubicin, which led to the suppression of NHEJ pathway.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available