combined inhibition of atr and wee1 as a novel therapeutic strategy in triple-negative breast cancer

Clicks: 117
ID: 211199
2018
Free PDF
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This article has not been analysed, so there is no overall score — reader engagement is measured and shown alongside.
AI Quality Assessment
Not analyzed
Readership in this journal
Emerging

Ranked #180 of 203 articles by views in ACS chemical neuroscience

Most read Least read

Bar heights use a square-root scale. Only the 120 most-read articles are drawn; the journal has 203 in total.

Mint this article as an NFT
Not yet minted

Create a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.

5 SUSD one-off · no wallet required
Sign in to mint
Abstract
Triple negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that poses a clinical challenge. Thus, new therapy strategies are urgently needed. The selective WEE1 inhibitor, AZD1775, has shown strong anti-proliferative effects on a variety of tumors. Here, we first demonstrate that inhibition of ATR by selective inhibitor AZD6738 can enhance AZD1775-caused growth inhibition in TNBC. Our results show that the enhanced cell death is attributed to repressed DNA damage repair and excessive replication stress, thereby causing increased DNA damage reflected by accumulation of the DNA double-strand-break marker γH2AX. On the other hand, combined treatment with AZD6738 and AZD1775 forces mitotic entry of cells with DNA damages by activating CDK1 activity, inducing severely aberrant mitosis and mitotic catastrophe, ultimately resulting in cell death. Dual inhibition of WEE1 and ATR also inactivated RAD51-mediated homologous recombination, which sensitized TNBC cells to cisplatin and PARP inhibitor. Here, based on the preclinical results that ATR inhibition synergizes with WEE1 inhibition in TNBC, we propose that this combination therapy alone, or in parallel with chemotherapy, represents an innovative and potent targeted therapy in TNBC.
Reference Key
jin2018neoplasia:combined Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Juan Jin;Hehui Fang;Fang Yang;Wenfei Ji;Nan Guan;Zijia Sun;Yaqin Shi;Guohua Zhou;Xiaoxiang Guan
Journal ACS chemical neuroscience
Year 2018
DOI
DOI not found
URL
http://www.sciencedirect.com/science/article/pii/S1476558618300800
Keywords
neoplasms Oncology including cancer and carcinogens tumors

Citations

No citations found. To add a citation, contact the admin at info@scimatic.org

Comments

No comments yet. Be the first to comment on this article.