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Tumour Hypoxia Affects the Responsiveness of Cancer Cells to Chemotherapy and Promotes Cancer Progression
Abstract
A solid tumour forms an organ-like structure that is comprised of cancer cells as well as stroma cells (fibroblasts, inflammatory cells) that are embedded in an extracellular matrix and are nourished by vascular network. However, tumoral microenvironment is heterogeneous due to the abnormal vasculature network and high proliferation rate of cancer cells. Because of these features, some regions are starved from oxygen, a phenomenon called hypoxia. Transient hypoxia is associated with inadequate blood flow while chronic hypoxia is the consequence of the increased oxygen diffusion distance due to tumour expansion. Both types of hypoxia are correlated with poor outcome for patients. Moreover, hypoxia also enhances chemoresistance of cancer cells. Firstly, the delivery of drugs in hypoxic area and cellular uptake of it are affected by hypoxia or associated acidity. Secondly, some chemotherapeutic drugs require oxygen to generate free radicals that contribute to cytotoxicity. Last, hypoxia induces cellular adaptations that compromise the effectiveness of chemotherapy. In response to nutrient deprivation due to hypoxia, the rate of proliferation of cancer cells decreases but chemotherapeutic drugs are more effective against proliferating cells. On the other hand, hypoxia induces adaptation by post-translational and transcriptional changes that promote cell survival and resistance to chemotherapy. Through these changes, hypoxia promotes angiogenesis, shift to glycolytic metabolism, expression of ABC transporters, cell survival by inducing the expression of genes encoding growth factors and the modulation of apoptotic process. The aim of this review is to provide a description of known hypoxia-induced mechanisms of chemoresistance at a cellular level.
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“Drug delivery and cellular uptake of drugs in hypoxic regions are known to be affected by hypoxia or associated acidity, resulting in the relative resistance of hypoxic tumor cells to chemotherapy. 376 , 377”
From Hypoxia signaling in cancer: Implications for therapeutic interventions (2023) · cites this paper as [376]
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Metadata
- Authors
- Cosse, J.-P., & Michiels, C.
- Affiliations
- University of Namur (BE)
- Corresponding author
- Michiels, Carine
- ORCID
- Michiels, Carine
- Venue
- Anti-Cancer Agents in Medicinal Chemistry
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2008-10-01
- Volume
- 8
- Issue
- 7
- Pages
- 790-797
- ISSN
- 1568-0118 (ISSN-L)
- 1871-5206
- OpenAlex
- W2044149912
- Cited by
- 348
- References
- 0
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 16 · 2023: 19 · 2022: 27 · 2021: 32 · 2020: 33 · 2019: 21 · 2018: 24 · 2017: 23 · 2016: 25 · 2015: 25 · 2014: 15 · 2013: 20 · 2012: 14
- FWCI
- 4.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Anti-Cancer Agents in Medicinal Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Libraries (submittedVersion)
- ORBi (University of Liège) (submittedVersion)
- Repository of the University of Namur (submittedVersion)
- Funders
- Fonds De La Recherche Scientifique - FNRS
- Fonds pour la Formation à la Recherche dans l’Industrie et dans l’Agriculture
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- tumor hypoxia, chemoresistance, tumor microenvironment, tumor stroma, tumor vasculature, transcriptional adaptation, angiogenesis, glycolytic metabolism, ABC transporters, apoptosis, tumor progression
- MeSH terms
- Animals, Autophagy, Humans, Neoplasm Invasiveness, Neoplasms, Neovascularization, Pathologic, Cell Hypoxia, Tumor Suppressor Protein p53, Disease Progression, Drug Resistance, Neoplasm, Proto-Oncogene Proteins c-bcl-2, Angiogenesis Inhibitors, Cell Proliferation, Hypoxia-Inducible Factor 1
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