Nature Communications (Feb 2017)
CX-5461 is a DNA G-quadruplex stabilizer with selective lethality in BRCA1/2 deficient tumours
- Hong Xu,
- Marco Di Antonio,
- Steven McKinney,
- Veena Mathew,
- Brandon Ho,
- Nigel J. O’Neil,
- Nancy Dos Santos,
- Jennifer Silvester,
- Vivien Wei,
- Jessica Garcia,
- Farhia Kabeer,
- Daniel Lai,
- Priscilla Soriano,
- Judit Banáth,
- Derek S. Chiu,
- Damian Yap,
- Daniel D. Le,
- Frank B. Ye,
- Anni Zhang,
- Kelsie Thu,
- John Soong,
- Shu-chuan Lin,
- Angela Hsin Chin Tsai,
- Tomo Osako,
- Teresa Algara,
- Darren N. Saunders,
- Jason Wong,
- Jian Xian,
- Marcel B. Bally,
- James D. Brenton,
- Grant W. Brown,
- Sohrab P. Shah,
- David Cescon,
- Tak W. Mak,
- Carlos Caldas,
- Peter C. Stirling,
- Phil Hieter,
- Shankar Balasubramanian,
- Samuel Aparicio
Affiliations
- Hong Xu
- Department of Molecular Oncology, and Department of Pathology and Laboratory Medicine, British Columbia Cancer Research Centre, University of British Columbia
- Marco Di Antonio
- Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Robinson Way,
- Steven McKinney
- Department of Molecular Oncology, and Department of Pathology and Laboratory Medicine, British Columbia Cancer Research Centre, University of British Columbia
- Veena Mathew
- Terry Fox Laboratory, BC Cancer Agency
- Brandon Ho
- Department of Biochemistry and Donnelly Centre, University of Toronto
- Nigel J. O’Neil
- Michael Smith Laboratories, University of British Columbia
- Nancy Dos Santos
- BC Cancer Agency and Department of Pathology and Laboratory Medicine, Advanced Therapeutics, University of British Columbia
- Jennifer Silvester
- Campbell Family Institute for Breast Cancer Research, Princess Margret Cancer Centre
- Vivien Wei
- Department of Molecular Oncology, and Department of Pathology and Laboratory Medicine, British Columbia Cancer Research Centre, University of British Columbia
- Jessica Garcia
- Department of Molecular Oncology, and Department of Pathology and Laboratory Medicine, British Columbia Cancer Research Centre, University of British Columbia
- Farhia Kabeer
- Department of Molecular Oncology, and Department of Pathology and Laboratory Medicine, British Columbia Cancer Research Centre, University of British Columbia
- Daniel Lai
- Department of Molecular Oncology, and Department of Pathology and Laboratory Medicine, British Columbia Cancer Research Centre, University of British Columbia
- Priscilla Soriano
- Department of Molecular Oncology, and Department of Pathology and Laboratory Medicine, British Columbia Cancer Research Centre, University of British Columbia
- Judit Banáth
- Department of Integrative Oncology, BC Cancer Agency
- Derek S. Chiu
- Department of Molecular Oncology, and Department of Pathology and Laboratory Medicine, British Columbia Cancer Research Centre, University of British Columbia
- Damian Yap
- Department of Molecular Oncology, and Department of Pathology and Laboratory Medicine, British Columbia Cancer Research Centre, University of British Columbia
- Daniel D. Le
- Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Robinson Way,
- Frank B. Ye
- Michael Smith Laboratories, University of British Columbia
- Anni Zhang
- Terry Fox Laboratory, BC Cancer Agency
- Kelsie Thu
- Campbell Family Institute for Breast Cancer Research, Princess Margret Cancer Centre
- John Soong
- Senhwa Biosciences, Inc.
- Shu-chuan Lin
- Senhwa Biosciences, Inc.
- Angela Hsin Chin Tsai
- Department of Molecular Oncology, and Department of Pathology and Laboratory Medicine, British Columbia Cancer Research Centre, University of British Columbia
- Tomo Osako
- Department of Molecular Oncology, and Department of Pathology and Laboratory Medicine, British Columbia Cancer Research Centre, University of British Columbia
- Teresa Algara
- Department of Molecular Oncology, and Department of Pathology and Laboratory Medicine, British Columbia Cancer Research Centre, University of British Columbia
- Darren N. Saunders
- Department of Molecular Oncology, and Department of Pathology and Laboratory Medicine, British Columbia Cancer Research Centre, University of British Columbia
- Jason Wong
- Department of Molecular Oncology, and Department of Pathology and Laboratory Medicine, British Columbia Cancer Research Centre, University of British Columbia
- Jian Xian
- Cancer Research UK Cambridge Research Institute and Department of Oncology, University of Cambridge, Li Ka Shing Centre
- Marcel B. Bally
- BC Cancer Agency and Department of Pathology and Laboratory Medicine, Advanced Therapeutics, University of British Columbia
- James D. Brenton
- Cancer Research UK Cambridge Research Institute and Department of Oncology, University of Cambridge, Li Ka Shing Centre
- Grant W. Brown
- Department of Biochemistry and Donnelly Centre, University of Toronto
- Sohrab P. Shah
- Department of Molecular Oncology, and Department of Pathology and Laboratory Medicine, British Columbia Cancer Research Centre, University of British Columbia
- David Cescon
- Campbell Family Institute for Breast Cancer Research, Princess Margret Cancer Centre
- Tak W. Mak
- Campbell Family Institute for Breast Cancer Research, Princess Margret Cancer Centre
- Carlos Caldas
- Cancer Research UK Cambridge Research Institute and Department of Oncology, University of Cambridge, Li Ka Shing Centre
- Peter C. Stirling
- Terry Fox Laboratory, BC Cancer Agency
- Phil Hieter
- Michael Smith Laboratories, University of British Columbia
- Shankar Balasubramanian
- Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Robinson Way,
- Samuel Aparicio
- Department of Molecular Oncology, and Department of Pathology and Laboratory Medicine, British Columbia Cancer Research Centre, University of British Columbia
- DOI
- https://doi.org/10.1038/ncomms14432
- Journal volume & issue
-
Vol. 8,
no. 1
pp. 1 – 18
Abstract
Stabilization of DNA quadruplex structures (G4) is lethal for cells with a compromised DNA repair pathway. Here, the authors show that CX-5461, a small molecule in clinical trials as RNA polymerase inhibitor, has G4-stablization properties and can be repurposed to target DNA repair-defective cancers cells.
