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Cited by 433Cancer, Hypoxia, and MetabolismRadiation Therapy and DosimetryAngiogenesis and VEGF in Cancer

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Targeting Hypoxia, HIF-1, and Tumor Glucose Metabolism to Improve Radiotherapy Efficacy

Meijer, Tineke W.H., Kaanders, Johannes H.A.M., Span, Paul N., Bussink, Johan·2012·Clinical Cancer Research
DOI 10.1158/1078-0432.ccr-12-0858
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Abstract

Radiotherapy, an important treatment modality in oncology, kills cells through induction of oxidative stress. However, malignant tumors vary in their response to irradiation as a consequence of resistance mechanisms taking place at the molecular level. It is important to understand these mechanisms of radioresistance, as counteracting them may improve the efficacy of radiotherapy. In this review, we describe how the hypoxia-inducible factor 1 (HIF-1) pathway has a profound effect on the response to radiotherapy. The main focus will be on HIF-1-controlled protection of the vasculature postirradiation and on HIF-1 regulation of glycolysis and the pentose phosphate pathway. This aberrant cellular metabolism increases the antioxidant capacity of tumors, thereby countering the oxidative stress caused by irradiation. From the results of translational studies and the first clinical phase I/II trials, it can be concluded that targeting HIF-1 and tumor glucose metabolism at several levels reduces the antioxidant capacity of tumors, affects the tumor microenvironment, and sensitizes various solid tumors to irradiation.

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  • HIF-1α-mediated alterations in tumor glucose metabolism may also affect cellular responses to IR.

    “HIF-1α-mediated alterations in tumor glucose metabolism may also affect cellular responses to IR (Meijer et al., 2012).”

    From Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer (2016) · cites this paper as Meijer et al., 2012

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Metadata

Authors
Meijer, T. W. H., Kaanders, J. H. A. M., Span, P. N., & Bussink, J.
Affiliations
Radboud University Medical Center (NL)
ORCID
Venue
Clinical Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2012-10-14
Volume
18
Issue
20
Pages
5585-5594
ISSN
  • 1078-0432 (ISSN-L)
  • 1557-3265
DOI
10.1158/1078-0432.ccr-12-0858
OpenAlex
W2116974984
Cited by
433
References
11
Citations by year
2026: 14 · 2025: 14 · 2024: 23 · 2023: 30 · 2022: 33 · 2021: 44 · 2020: 30 · 2019: 36 · 2018: 27 · 2017: 38 · 2016: 46 · 2015: 34 · 2014: 43 · 2013: 17 · 2012: 4
FWCI
2.27
Type
journal article
Language
en
Open access
closed
Locations
  • Clinical Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
  • Radboud Repository (Radboud University) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Physical Sciences › Physics and Astronomy › Radiation › Radiation Therapy and Dosimetry
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Keywords
radioresistance (biology), HIF-1, tumor hypoxia, tumor glucose metabolism, glycolysis, pentose phosphate pathway, oxidative stress, antioxidant capacity, tumor vasculature, tumor microenvironment, radiosensitization, radiotherapy efficacy
MeSH terms
Glucose, Humans, Neoplasms, Neovascularization, Pathologic, Radiation Tolerance, Signal Transduction, Cell Hypoxia, Hypoxia-Inducible Factor 1, alpha Subunit, Molecular Targeted Therapy, Tumor Microenvironment

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