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 accessAbstract
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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Citations
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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
- Published
- 2017-02-17
- Volume
- 8
- Issue
- 1
- Pages
- 14432-14432
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2588267243
- Cited by
- 580
- References
- 55
- FWCI
- 17.28
- Type
- journal article
- Language
- en
- Open access
- gold
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