Genome-wide synthetic lethal screen unveils novel CAIX-NFS1/xCT axis as a targetable vulnerability in hypoxic solid tumors

Author:

Chafe Shawn C.1ORCID,Vizeacoumar Frederick S.2ORCID,Venkateswaran Geetha1ORCID,Nemirovsky Oksana1,Awrey Shannon1ORCID,Brown Wells S.1,McDonald Paul C.1ORCID,Carta Fabrizio3ORCID,Metcalfe Andrew4ORCID,Karasinska Joanna M.4ORCID,Huang Ling5ORCID,Muthuswamy Senthil K.5ORCID,Schaeffer David F.46,Renouf Daniel J.47,Supuran Claudiu T.3ORCID,Vizeacoumar Franco J.89,Dedhar Shoukat110ORCID

Affiliation:

1. Department of Integrative Oncology, BC Cancer Research Institute, Vancouver, BC V5Z 1L3, Canada.

2. Department of Pathology and Laboratory Medicine, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 0W8, Canada.

3. NEUROFARBA Department, University of Florence, Via U. Schiff 6, Florence 50019, Italy.

4. Pancreas Centre BC, Vancouver, BC V3Z 1M9, Canada.

5. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

6. Department of Pathology and Laboratory Medicine, Vancouver General Hospital, Vancouver, BC V5Z 1M9, Canada.

7. Medical Oncology, BC Cancer, Vancouver, BC V5Z 4E67, Canada.

8. Division of Oncology, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 0W8, Canada.

9. Cancer Research Department, Saskatchewan Cancer Agency, Saskatoon, SK S7N 4E5, Canada.

10. Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.

Abstract

Targeting carbonic anhydrase IX acidifies intracellular pH, disrupts redox homeostasis, and creates vulnerability to ferroptosis.

Funder

Canadian Cancer Society Research Institute

Canadian Institutes of Health Research

Canadian Foundation for Innovation

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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