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Future Med Chem. 2018 Sep 1;10(18):2227-2236. doi: 10.4155/fmc-2018-0163. Epub 2018 Aug 9.

Hypoxia-inducible factor 2α: a novel target in gliomas.

Author information

1
Department of Neurological Surgery, Wake Forest Baptist Medical Center, Winston-Salem, NC 27157, USA.
2
Brain Tumor Center of Excellence, Wake Forest Comprehensive Cancer Center, Winston-Salem, NC 27157, USA.
3
Department of Radiation Oncology, Wake Forest Baptist Medical Center, Winston-Salem, NC 27157, USA.
4
Department of Cancer Biology, Wake Forest Baptist Medical Center, Winston-Salem, NC 27157, USA.
5
Department of Pathology, Wake Forest Baptist Medical Center, Winston-Salem, NC27157, USA.
6
Foundation Medicine, Inc., Morrisville, NC 27560, USA.
7
Department of Radiation Oncology, Mayo Clinic, Rochester, MN 55905, USA.
8
Department of Internal Medicine, Section on Hematology & Oncology, Wake Forest Baptist Medical Center, Winston-Salem, NC 27157, USA.
9
Department of Neurology, Wake Forest Baptist Medical Center, Winston-Salem, NC 27157, USA.

Abstract

Hypoxia is an important contributor to aggressive behavior and resistance mechanisms in glioblastoma. Upregulation of hypoxia inducible transcription factors (HIFs) is the primary adaptive cellular response to a hypoxic environment. While HIF1α has been widely studied in cancer, HIF2α offers a potentially more specific and appealing target in glioblastoma given expression in glioma stem cells and not normal neural progenitors, activation in states of chronic hypoxia and expression that correlates with glioma patient survival. A first-in-class HIF2α inhibitor, PT2385, is in clinical trials for renal cell carcinoma, and provides the first opportunity to therapeutically target this important pathway in glioma biology.

KEYWORDS:

cancer; glioblastoma; hypoxia; hypoxia-inducible factors

PMID:
30089425
PMCID:
PMC6479274
DOI:
10.4155/fmc-2018-0163
[Indexed for MEDLINE]
Free PMC Article

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