Abstract
Hypoxia is one of the most common phenotypes of malignant tumours. Hypoxia leads to the increased activity of hypoxia-inducible factors (HIFs), which regulate the expression of genes controlling a raft of pro-tumour phenotypes. These include maintenance of the cancer stem cell compartment, epithelial-mesenchymal transition (EMT), angiogenesis, immunosuppression, and metabolic reprogramming. Hypoxia can also contribute to the tumour progression in a HIF-independent manner via the activation of a complex signalling network pathway, including JAK-STAT, RhoA/ROCK, NF-κB and PI3/AKT. Recent studies suggest that nanotherapeutics offer a unique opportunity to target the hypoxic microenvironment, enhancing the therapeutic window of conventional therapeutics. In this review, we summarise recent advances in understanding the impact of hypoxia on tumour progression, while outlining possible nanotherapeutic approaches for overcoming hypoxia-mediated resistance.
Highlights
The hostile microenvironment within a solid tumour is increasingly recognized as a major impediment to effective cancer therapy [1]
Tumour hypoxia is a critical feature of the tumour microenvironment (TME), contributing to disease progression and resistance to chemo and radiotherapy
The response to tumour hypoxia is mainly driven by oxygen-dependent
Summary
The hostile microenvironment within a solid tumour is increasingly recognized as a major impediment to effective cancer therapy [1]. A hallmark of malignancy, is one of the most typical and important features of the tumour microenvironment (TME), caused by the imbalance between oxygen supply and consumption by cancer and stromal cells [2,3]. Failure of the local environment to overcome this deficit due to the aberrant vascular architecture results in tumour hypoxia. Hypoxia has been shown to contribute to malignant progression and treatment failure, in particular, resistance to radiotherapy
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