Monitoring the dynamics of Src activity in response to anti-invasive dasatinib treatment at a subcellular level using dual intravital imaging

Nobis, M., McGhee, E. J., Herrmann, D., Magenau, A., Morton, J. P., Anderson, K. I. and Timpson, P. (2014) Monitoring the dynamics of Src activity in response to anti-invasive dasatinib treatment at a subcellular level using dual intravital imaging. Cell Adhesion and Migration, 8(5), pp. 478-486. (doi: 10.4161/19336918.2014.970004)

[img]
Preview
Text
102905.pdf - Published Version
Available under License Creative Commons Attribution Non-commercial.

1MB

Abstract

Optimising response to tyrosine kinase inhibitors in cancer remains an extensive field of research. Intravital imaging is an emerging tool, which can be used in drug discovery to facilitate and fine-tune maximum drug response in live tumors. A greater understanding of intratumoural delivery and pharmacodynamics of a drug can be obtained by imaging drug target-specific fluorescence resonance energy transfer (FRET) biosensors in real time. Here, we outline our recent work using a Src-FRET biosensor as a readout of Src activity to gauge optimal tyrosine kinase inhibition in response to dasatinib treatment regimens in vivo. By simultaneously monitoring both the inhibition of Src using FRET imaging, and the modulation of the surrounding extracellular matrix using second harmonic generation (SHG) imaging, we were able to show enhanced drug penetrance and delivery to live pancreatic tumors. We discuss the implications of this dual intravital imaging approach in the context of altered tumor-stromal interactions, while summarising how this approach could be applied to assess other combination strategies or tyrosine kinase inhibitors in a preclinical setting.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Anderson, Professor Kurt and McGhee, Dr Ewan and Timpson, Dr Paul and Nobis, Mr Max and Morton, Professor Jen
Authors: Nobis, M., McGhee, E. J., Herrmann, D., Magenau, A., Morton, J. P., Anderson, K. I., and Timpson, P.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Cell Adhesion and Migration
Publisher:Taylor and Francis
ISSN:1933-6918
ISSN (Online):1933-6926
Copyright Holders:Copyright © 2014 The Authors
First Published:First published in Cell Adhesion and Migration 8(5):478-486
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record