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Cited by 580

The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.

CX-5461 is a DNA G-quadruplex stabilizer with selective lethality in BRCA1/2 deficient tumours

Open access
Xu, Hong, Di Antonio, Marco, McKinney, Steven, Mathew, Veena, Ho, Brandon, O’Neil, Nigel J., Santos, Nancy Dos, Silvester, Jennifer, Wei, Vivien, Garcia, Jessica, Kabeer, Farhia, Lai, Daniel, Soriano, Priscilla, Banáth, Judit, Chiu, Derek S., Yap, Damian, Le, Daniel D., Ye, Frank B., Zhang, Anni, Thu, Kelsie, Soong, John, Lin, Shu-chuan, Tsai, Angela Hsin Chin, Osako, Tomo, Algara, Teresa, Saunders, Darren N., Wong, Jason, Xian, Jian, Bally, Marcel B., Brenton, James D., Brown, Grant W., Shah, Sohrab P., Cescon, David, Mak, Tak W., Caldas, Carlos, Stirling, Peter C., Hieter, Phil, Balasubramanian, Shankar, Aparicio, Samuel·2017·Nature Communications
DOI 10.1038/ncomms14432
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Abstract

G-quadruplex DNAs form four-stranded helical structures and are proposed to play key roles in different cellular processes. Targeting G-quadruplex DNAs for cancer treatment is a very promising prospect. Here, we show that CX-5461 is a G-quadruplex stabilizer, with specific toxicity against BRCA deficiencies in cancer cells and polyclonal patient-derived xenograft models, including tumours resistant to PARP inhibition. Exposure to CX-5461, and its related drug CX-3543, blocks replication forks and induces ssDNA gaps or breaks. The BRCA and NHEJ pathways are required for the repair of CX-5461 and CX-3543-induced DNA damage and failure to do so leads to lethality. These data strengthen the concept of G4 targeting as a therapeutic approach, specifically for targeting HR and NHEJ deficient cancers and other tumours deficient for DNA damage repair. CX-5461 is now in advanced phase I clinical trial for patients with BRCA1/2 deficient tumours (Canadian trial, NCT02719977, opened May 2016).

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Metadata

Authors
Xu, H., Di Antonio, M., McKinney, S., Mathew, V., Ho, B., O’Neil, N. J., Santos, N. D., Silvester, J., Wei, V., Garcia, J., Kabeer, F., Lai, D., Soriano, P., Banáth, J., Chiu, D. S., Yap, D., Le, D. D., Ye, F. B., Zhang, A., Thu, K., Soong, J., Lin, S.-C., Tsai, A. H. C., Osako, T., Algara, T., Saunders, D. N., Wong, J., Xian, J., Bally, M. B., Brenton, J. D., Brown, G. W., Shah, S. P., Cescon, D., Mak, T. W., Caldas, C., Stirling, P. C., Hieter, P., Balasubramanian, S., & Aparicio, S.
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2017-02-17
Volume
8
Issue
1
Pages
14432-14432
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/ncomms14432
OpenAlex
W2588267243
Cited by
580
References
55
FWCI
17.28
Type
journal article
Language
en
Open access
gold

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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