KFU. Card publication. Synthetic Lethal Targeting of Mitotic Checkpoints in HPV-Negative Head and Neck Cancer

KAZAN
FEDERAL UNIVERSITY

- RUS
- 中文
- ES

SYNTHETIC LETHAL TARGETING OF MITOTIC CHECKPOINTS IN HPV-NEGATIVE HEAD AND NECK CANCER

Form of presentation

Articles in international journals and collections

Year of publication

2020

��

��

Authors, employees of KFU

Deneka Aleksandr Yaroslavovich, author

Other authors

Bennett John , author

Burtness Barbara , author

Einarson Margret , author

Elmekawy Mohamed , author

Golemis Erica , author

Lee Jong Woo , author

Nikonova Anna , author

Zhou Yan , author

Bibliographic description in the original language

Deneka A.Y. Synthetic Lethal Targeting of Mitotic Checkpoints in HPV-Negative Head and Neck Cancer / A.Y. Deneka, M.B. Einarson, J. Bennett, A.S. Nikonova, M. Elmekawy, Y. Zhou, J.W. Lee, B.A. Burtness, E.A. Golemis // Cancers.-2020. - V.12, doi: doi:10.3390/cancers12020306

Annotation

Cancers

Keywords

prexasertib; adavosertib; mitotic catastrophe; head and neck cancer

The name of the journal

Cancers

Please use this ID to quote from or refer to the card

https://repository.kpfu.ru/eng/?p_id=220758&p_lang=2

Resource files

File name	Size (MB)	Format
13.__NSCC_Screen_Cancers.pdf	2,54	pdf	show / download

Full metadata record

Field DC	Value	Language
dc.contributor.author	Deneka Aleksandr Yaroslavovich	ru_RU
dc.contributor.author	Bennett John	ru_RU
dc.contributor.author	Burtness Barbara	ru_RU
dc.contributor.author	Einarson Margret	ru_RU
dc.contributor.author	Elmekawy Mohamed	ru_RU
dc.contributor.author	Golemis Erica	ru_RU
dc.contributor.author	Lee Jong Woo	ru_RU
dc.contributor.author	Nikonova Anna	ru_RU
dc.contributor.author	Zhou Yan	ru_RU
dc.date.accessioned	2020-01-01T00:00:00Z	ru_RU
dc.date.available	2020-01-01T00:00:00Z	ru_RU
dc.date.issued	2020	ru_RU
dc.identifier.citation	Deneka A.Y. Synthetic Lethal Targeting of Mitotic Checkpoints in HPV-Negative Head and Neck Cancer / A.Y. Deneka, M.B. Einarson, J. Bennett, A.S. Nikonova, M. Elmekawy, Y. Zhou, J.W. Lee, B.A. Burtness, E.A. Golemis // Cancers.-2020. - V.12, doi: doi:10.3390/cancers12020306	ru_RU
dc.identifier.uri	https://repository.kpfu.ru/eng/?p_id=220758&p_lang=2	ru_RU
dc.description.abstract	Cancers	ru_RU
dc.description.abstract	Head and neck squamous cell carcinomas (HNSCC) affect more than 800,000 people annually worldwide, causing over 15,000 deaths in the US. Among HNSCC cancers, human papillomavirus (HPV)-negative HNSCC has the worst outcome, motivating efforts to improve therapy for this disease. The most common mutational events in HPV-negative HNSCC are inactivation of the tumor suppressors TP53 (>85%) and CDKN2A (>57%), which significantly impairs G1/S checkpoints, causing reliance on other cell cycle checkpoints to repair ongoing replication damage. We evaluated a panel of cell cycle-targeting clinical agents in a group of HNSCC cell lines to identify a subset of drugs with single-agent activity in reducing cell viability. Subsequent analyses demonstrated potent combination activity between the CHK1/2 inhibitor LY2606268 (prexasertib), which eliminates a G2 checkpoint, and the WEE1 inhibitor AZD1775 (adavosertib), which promotes M-phase entry, in induction of DNA damage, mitotic catastrophe, and apoptosis, and reduction of anchorage independent growth and clonogenic capacity. These phenotypes were accompanied by more significantly reduced activation of CHK1 and its paralog CHK2, and enhanced CDK1 activation, eliminating breaks on the mitotic entry of cells with DNA damage. These data suggest the potential value of dual inhibition of CHK1 and WEE1 in tumors with compromised G1/S checkpoints.	ru_RU
dc.language.iso	ru	ru_RU
dc.subject		ru_RU
dc.title	Synthetic Lethal Targeting of Mitotic Checkpoints in HPV-Negative Head and Neck Cancer	ru_RU
dc.type	Articles in international journals and collections	ru_RU