Journal article
Small-Molecule Inhibitors Targeting DNA Repair and DNA Repair Deficiency in Research and Cancer Therapy
CELL CHEMICAL BIOLOGY, Vol.24(9), pp.1101-1119
09/21/2017
DOI: 10.1016/j.chembiol.2017.08.027
PMCID: PMC5679738
PMID: 28938088
Abstract
To maintain stable genomes and to avoid cancer and aging, cells need to repair a multitude of deleterious DNA lesions, which arise constantly in every cell. Processes that support genome integrity in normal cells, however, allow cancer cells to develop resistance to radiation and DNA-damaging chemotherapeutics. Chemical inhibition of the key DNA repair proteins and pharmacologically induced synthetic lethality have become instrumental in both dissecting the complex DNA repair networks and as promising anticancer agents. The difficulty in capitalizing on synthetically lethal interactions in cancer cells is that many potential targets do not possess well-defined small-molecule binding determinates. In this review, we discuss several successful campaigns to identify and leverage small-molecule inhibitors of the DNA repair proteins, from PARP1, a paradigm case for clinically successful small-molecule inhibitors, to coveted new targets, such as RAD51 recombinase, RAD52 DNA repair protein, MRE11 nuclease, and WRN DNA helicase.
Details
- Title: Subtitle
- Small-Molecule Inhibitors Targeting DNA Repair and DNA Repair Deficiency in Research and Cancer Therapy
- Creators
- Sarah R. Hengel - University of IowaM. Ashley Spies - University of IowaMaria Spies - University of Iowa
- Resource Type
- Journal article
- Publication Details
- CELL CHEMICAL BIOLOGY, Vol.24(9), pp.1101-1119
- DOI
- 10.1016/j.chembiol.2017.08.027
- PMID
- 28938088
- PMCID
- PMC5679738
- NLM abbreviation
- Cell Chem Biol
- ISSN
- 2451-9448
- eISSN
- 2451-9448
- Publisher
- Elsevier
- Number of pages
- 19
- Grant note
- P30CA086862 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) NIH P30 CA086862 / University of Iowa Holden Comprehensive Cancer Center R01GM108617 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) R01 GM108617; R01-GM097373 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 09/21/2017
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Radiation Oncology; Biochemistry and Molecular Biology; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984288720202771
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