Browse by author
Lookup NU author(s): Professor Steve Wedge
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2017 The Author(s). Although an array of new therapeutics has emerged for the treatment of colorectal cancer, their use is significantly impacted by variability in patient response. Better pre-clinical models could substantially improve efficacy as it may allow stratification of patients into the correct treatment regime. Here we explore acute, ex vivo treatment of fresh, surgically resected human colorectal tumour biopsies as a novel pre-clinical model for identifying patient response to specific therapeutics. The MEK1/2 inhibitor, Selumetinib (AZD6244, ARRY-142886) was used as a tool compound. Firstly, we established an acute treatment protocol and demonstrated this protocol could differentiate phenotypic and pharmacodynamic responses to Selumetinib (0-3uM). We then used the protocol to evaluate Selumetinib response in tumours from 23 colon cancer patients. These studies revealed that the agent inhibited pERK1/2 phosphorylation in all tumours, caused a significant decrease in proliferation in 5/23 (22%) tumours, and that KRAS/BRAF mutant tumours were particularly sensitive to the anti-proliferative effects of the agent. These data are consistent with data from clinical trials of Selumetinib, suggesting that acute treatment of small tumour biopsies is worthy of further exploration as a pre-clinical model to evaluate colorectal cancer response to novel therapies.
Author(s): Novo SM, Wedge SR, Stark LA
Publication type: Article
Publication status: Published
Journal: Scientific Reports
Year: 2017
Volume: 7
Issue: 1
Online publication date: 20/09/2017
Acceptance date: 06/09/2017
Date deposited: 20/10/2017
ISSN (electronic): 2045-2322
Publisher: Nature Publishing Group
URL: https://doi.org/10.1038/s41598-017-12222-9
DOI: 10.1038/s41598-017-12222-9
Altmetrics provided by Altmetric
