Addressing the tumour microenvironment in early drug discovery: a strategy to overcome drug resistance and identify novel targets for cancer therapy
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Loessner, Daniela
Avery, Vicky M
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Abstract
The tumour microenvironment (TME) comprises not only malignant and non-malignant cells, but also the extracellular matrix (ECM), secreted factors, and regulators of cellular functions. In addition to genetic alterations, changes of the biochemical/biophysical properties or cellular composition of the TME have been implicated in drug resistance. Here, we review the composition of the ECM and different elements of the TME contributing to drug resistance, including soluble factors, hypoxia, extracellular acidity, and cell adhesion properties. We discuss selected approaches for modelling the TME, current progress, and their use in low-and high-throughput assays for preclinical studies. Lastly, we summarise the status quo of advanced 3D cancer models compatible with high-throughput screening (HTS), the technical practicalities and challenges.
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Drug Discovery Today
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This publication has been entered as an advanced online version in Griffith Research Online.
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Biochemistry and cell biology
Pharmacology and pharmaceutical sciences
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Kaemmerer, E; Loessner, D; Avery, VM, Addressing the tumour microenvironment in early drug discovery: a strategy to overcome drug resistance and identify novel targets for cancer therapy, Drug Discovery Today, 2020