BRCA1 or CDK12 loss sensitizes cells to CHK1 inhibitors
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F17%3A00067247" target="_blank" >RIV/00159816:_____/17:00067247 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14310/17:00097945 RIV/61989592:15110/17:73584999 RIV/00027162:_____/17:N0000131
Result on the web
<a href="http://dx.doi.org/10.1177/1010428317727479" target="_blank" >http://dx.doi.org/10.1177/1010428317727479</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1177/1010428317727479" target="_blank" >10.1177/1010428317727479</a>
Alternative languages
Result language
angličtina
Original language name
BRCA1 or CDK12 loss sensitizes cells to CHK1 inhibitors
Original language description
A broad spectrum of tumors develop resistance to classic chemotherapy, necessitating the discovery of new therapies. One successful strategy exploits the synthetic lethality between poly(ADP-ribose) polymerase 1/2 proteins and DNA damage response genes, including BRCA1, a factor involved in homologous recombination-mediated DNA repair, and CDK12, a transcriptional kinase known to regulate the expression of DDR genes. CHK1 inhibitors have been shown to enhance the anti-cancer effect of DNA-damaging compounds. Since loss of BRCA1 increases replication stress and leads to DNA damage, we tested a hypothesis that CDK12- or BRCA1-depleted cells rely extensively on S-phase-related CHK1 functions for survival. The silencing of BRCA1 or CDK12 sensitized tumor cells to CHK1 inhibitors in vitro and in vivo. BRCA1 downregulation combined with CHK1 inhibition induced excessive amounts of DNA damage, resulting in an inability to complete the S-phase. Therefore, we suggest CHK1 inhibition as a strategy for targeting BRCA1- or CDK12-deficient tumors.
Czech name
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Czech description
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Classification
Type
J<sub>ost</sub> - Miscellaneous article in a specialist periodical
CEP classification
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OECD FORD branch
30204 - Oncology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Tumor Biology
ISSN
1010-4283
e-ISSN
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Volume of the periodical
39
Issue of the periodical within the volume
10
Country of publishing house
NL - THE KINGDOM OF THE NETHERLANDS
Number of pages
11
Pages from-to
1-11
UT code for WoS article
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EID of the result in the Scopus database
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