DNA damage response in brain tumors: A Society for Neuro-Oncology consensus review on mechanisms and translational efforts in neuro-oncology

Author:

Rahman Rifaquat1,Shi Diana D1,Reitman Zachary J2,Hamerlik Petra3,de Groot John F4,Haas-Kogan Daphne A1,D’Andrea Alan D1,Sulman Erik P5,Tanner Kirk6,Agar Nathalie Y R7,Sarkaria Jann N8,Tinkle Christopher L9,Bindra Ranjit S10,Mehta Minesh P11,Wen Patrick Y12ORCID

Affiliation:

1. Department of Radiation Oncology, Brigham and Women’s Hospital, Harvard Medical School , Boston, Massachusetts , USA

2. Department of Radiation Oncology, Duke University Medical Center , Durham, North Carolina , USA

3. Division of Cancer Sciences, University of Manchester , Manchester , UK

4. Division of Neuro-Oncology, University of California San Francisco , San Francisco, California , USA

5. Department of Radiation Oncology, New York University , New York, New York , USA

6. National Brain Tumor Society , Newton, Massachusetts , USA

7. Department of Neurosurgery and Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School , Boston, Massachusetts , USA

8. Department of Radiation Oncology, Mayo Clinic , Rochester, Minnesota , USA

9. Department of Radiation Oncology, St. Jude Children’s Research Hospital , Memphis, Tennessee , USA

10. Department of Therapeutic Radiology, Yale University , New Haven, Connecticut , USA

11. Miami Cancer Institute, Baptist Hospital , Miami, Florida , USA

12. Center for Neuro-Oncology, Dana-Farber Cancer Institute, Harvard Medical School , Boston, Massachusetts , USA

Abstract

Abstract DNA damage response (DDR) mechanisms are critical to maintenance of overall genomic stability, and their dysfunction can contribute to oncogenesis. Significant advances in our understanding of DDR pathways have raised the possibility of developing therapies that exploit these processes. In this expert-driven consensus review, we examine mechanisms of response to DNA damage, progress in development of DDR inhibitors in IDH-wild-type glioblastoma and IDH-mutant gliomas, and other important considerations such as biomarker development, preclinical models, combination therapies, mechanisms of resistance and clinical trial design considerations.

Publisher

Oxford University Press (OUP)

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