2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity-Reference-Cited by-同舟云学术

2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity

Published:2017-02 Issue:375 Volume:9 Page:
ISSN:1946-6234
Container-title:Science Translational Medicine
language:en
Short-container-title:Sci. Transl. Med.

Author:

Sulkowski Parker L.¹²,Corso Christopher D.¹,Robinson Nathaniel D.¹,Scanlon Susan E.¹³,Purshouse Karin R.¹,Bai Hanwen²,Liu Yanfeng¹,Sundaram Ranjini K.¹,Hegan Denise C.¹,Fons Nathan R.¹³,Breuer Gregory A.¹³,Song Yuanbin⁴,Mishra-Gorur Ketu⁵,De Feyter Henk M.⁶,de Graaf Robin A.⁶,Surovtseva Yulia V.⁷,Kachman Maureen⁸,Halene Stephanie⁴,Günel Murat²⁵,Glazer Peter M.¹²,Bindra Ranjit S.¹³

Affiliation:

1. Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA.

2. Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA.

3. Department of Experimental Pathology, Yale University School of Medicine, New Haven, CT 06520, USA.

4. Section of Hematology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.

5. Department of Neurosurgery, Yale University School of Medicine, New Haven, CT 06520, USA.

6. Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT 06520, USA.

7. Yale Center for Molecular Discovery, West Haven, CT 06516, USA.

8. Michigan Regional Comprehensive Metabolomics Resource Core, National Institute of Environmental Health Sciences (NIEHS) Children’s Health Exposure Analysis Resource for Metabolomics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.

Abstract

The oncometabolite 2-hydroxyglutarate renders IDH1/2 mutant cancer cells deficient in homologous recombination and confers vulnerability to synthetic lethal targeting with PARP inhibitors.

Funder

NIH

American Cancer Society

Connecticut Department of Public Health

NIH Medical Scientist Program Training

NIH National Institute of General Medical Sciences

NIH Common Funds

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine

Reference71 articles.