Addressing the tumour microenvironment in early drug discovery: a strategy to overcome drug resistance and identify novel targets for cancer therapy

Elke Kaemmerer; Daniela Loessner; Vicky M Avery

doi:10.1016/j.drudis.2020.11.030

Addressing the tumour microenvironment in early drug discovery: a strategy to overcome drug resistance and identify novel targets for cancer therapy

Drug Discov Today. 2021 Mar;26(3):663-676. doi: 10.1016/j.drudis.2020.11.030. Epub 2020 Dec 2.

Authors

Elke Kaemmerer¹, Daniela Loessner², Vicky M Avery³

Affiliations

¹ Discovery Biology, Griffith University, Nathan, QLD, Australia; Cancer Therapeutics CRC, Griffith University, Nathan, QLD, Australia.
² Centre for Tumour Microenvironment, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Chemical Engineering and Department of Materials Science and Engineering, Faculty of Engineering, Monash University, Melbourne, VIC, Australia; Department of Anatomy and Developmental Biology, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia.
³ Discovery Biology, Griffith University, Nathan, QLD, Australia; Cancer Therapeutics CRC, Griffith University, Nathan, QLD, Australia; School of Environment & Science, Griffith University, QLD, Australia. Electronic address: v.avery@griffith.edu.au.

PMID: 33278601
DOI: 10.1016/j.drudis.2020.11.030

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.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Antineoplastic Agents / pharmacology*
Drug Discovery / methods*
Drug Evaluation, Preclinical / methods
Drug Resistance, Neoplasm
Extracellular Matrix / metabolism
High-Throughput Screening Assays
Humans
Models, Biological
Molecular Targeted Therapy
Neoplasms / drug therapy*
Tumor Microenvironment

Substances

Antineoplastic Agents