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Tumour-on-chip microfluidic platform for assessment of drug pharmacokinetics and treatment response

Microphysiological in vitro systems are platforms for preclinical evaluation of drug effects and significant advances have been made in recent years. However, existing microfluidic devices are not yet able to deliver compounds to cell models in a way that reproduces the real physiological drug expos...

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Autores principales: Petreus, Tudor, Cadogan, Elaine, Hughes, Gareth, Smith, Aaron, Pilla Reddy, Venkatesh, Lau, Alan, O’Connor, Mark James, Critchlow, Susan, Ashford, Marianne, Oplustil O’Connor, Lenka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385015/
https://www.ncbi.nlm.nih.gov/pubmed/34429505
http://dx.doi.org/10.1038/s42003-021-02526-y
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author Petreus, Tudor
Cadogan, Elaine
Hughes, Gareth
Smith, Aaron
Pilla Reddy, Venkatesh
Lau, Alan
O’Connor, Mark James
Critchlow, Susan
Ashford, Marianne
Oplustil O’Connor, Lenka
author_facet Petreus, Tudor
Cadogan, Elaine
Hughes, Gareth
Smith, Aaron
Pilla Reddy, Venkatesh
Lau, Alan
O’Connor, Mark James
Critchlow, Susan
Ashford, Marianne
Oplustil O’Connor, Lenka
author_sort Petreus, Tudor
collection PubMed
description Microphysiological in vitro systems are platforms for preclinical evaluation of drug effects and significant advances have been made in recent years. However, existing microfluidic devices are not yet able to deliver compounds to cell models in a way that reproduces the real physiological drug exposure. Here, we introduce a novel tumour-on-chip microfluidic system that mimics the pharmacokinetic profile of compounds on 3D tumour spheroids to evaluate their response to the treatments. We used this platform to test the response of SW620 colorectal cancer spheroids to irinotecan (SN38) alone and in combination with the ATM inhibitor AZD0156, using concentrations mimicking mouse plasma exposure profiles of both agents. We explored spheroid volume and viability as a measure of cancer cells response and changes in mechanistically relevant pharmacodynamic biomarkers (γH2AX, cleaved-caspase 3 and Ki67). We demonstrate here that our microfluidic tumour-on-chip platform can successfully predict the efficacy from in vivo studies and therefore represents an innovative tool to guide drug dose and schedules for optimal efficacy and pharmacodynamic assessment, while reducing the need for animal studies.
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spelling pubmed-83850152021-09-22 Tumour-on-chip microfluidic platform for assessment of drug pharmacokinetics and treatment response Petreus, Tudor Cadogan, Elaine Hughes, Gareth Smith, Aaron Pilla Reddy, Venkatesh Lau, Alan O’Connor, Mark James Critchlow, Susan Ashford, Marianne Oplustil O’Connor, Lenka Commun Biol Article Microphysiological in vitro systems are platforms for preclinical evaluation of drug effects and significant advances have been made in recent years. However, existing microfluidic devices are not yet able to deliver compounds to cell models in a way that reproduces the real physiological drug exposure. Here, we introduce a novel tumour-on-chip microfluidic system that mimics the pharmacokinetic profile of compounds on 3D tumour spheroids to evaluate their response to the treatments. We used this platform to test the response of SW620 colorectal cancer spheroids to irinotecan (SN38) alone and in combination with the ATM inhibitor AZD0156, using concentrations mimicking mouse plasma exposure profiles of both agents. We explored spheroid volume and viability as a measure of cancer cells response and changes in mechanistically relevant pharmacodynamic biomarkers (γH2AX, cleaved-caspase 3 and Ki67). We demonstrate here that our microfluidic tumour-on-chip platform can successfully predict the efficacy from in vivo studies and therefore represents an innovative tool to guide drug dose and schedules for optimal efficacy and pharmacodynamic assessment, while reducing the need for animal studies. Nature Publishing Group UK 2021-08-24 /pmc/articles/PMC8385015/ /pubmed/34429505 http://dx.doi.org/10.1038/s42003-021-02526-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Petreus, Tudor
Cadogan, Elaine
Hughes, Gareth
Smith, Aaron
Pilla Reddy, Venkatesh
Lau, Alan
O’Connor, Mark James
Critchlow, Susan
Ashford, Marianne
Oplustil O’Connor, Lenka
Tumour-on-chip microfluidic platform for assessment of drug pharmacokinetics and treatment response
title Tumour-on-chip microfluidic platform for assessment of drug pharmacokinetics and treatment response
title_full Tumour-on-chip microfluidic platform for assessment of drug pharmacokinetics and treatment response
title_fullStr Tumour-on-chip microfluidic platform for assessment of drug pharmacokinetics and treatment response
title_full_unstemmed Tumour-on-chip microfluidic platform for assessment of drug pharmacokinetics and treatment response
title_short Tumour-on-chip microfluidic platform for assessment of drug pharmacokinetics and treatment response
title_sort tumour-on-chip microfluidic platform for assessment of drug pharmacokinetics and treatment response
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385015/
https://www.ncbi.nlm.nih.gov/pubmed/34429505
http://dx.doi.org/10.1038/s42003-021-02526-y
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