BRCA1 or CDK12 loss sensitizes cells to CHK1 inhibitors

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00027162%3A_____%2F17%3AN0000131" target="_blank" >RIV/00027162:_____/17:N0000131 - isvavai.cz</a>

Alternative codes found

RIV/00159816:_____/17:00067247 RIV/00216224:14310/17:00097945 RIV/61989592:15110/17:73584999

Result on the web

<a href="http://journals.sagepub.com/doi/10.1177/1010428317727479" target="_blank" >http://journals.sagepub.com/doi/10.1177/1010428317727479</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1177/1010428317727479" target="_blank" >10.1177/1010428317727479</a>

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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Type

J_SC - Article in a specialist periodical, which is included in the SCOPUS database

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

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)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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

GB - UNITED KINGDOM

Number of pages

11

Pages from-to

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UT code for WoS article

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EID of the result in the Scopus database

2-s2.0-85031757280