Advanced intravital subcellular imaging reveals vital three-dimensional signalling events driving cancer cell behaviour and drug responses in live tissue

Abstract

The integration of signal transduction pathways plays a fundamental role in governing disease initiation, progression and outcome. It is therefore necessary to understand disease at the signalling level to enable effective treatment and to intervene in its progression. The recent extension of in vitro subcellular image-based analysis to live in vivo modelling of disease is providing a more complete picture of real-time, dynamic signalling processes or drug responses in live tissue. Intravital imaging offers alternative strategies for studying disease and embraces the biological complexities that govern disease progression. In the present review, we highlight how three-dimensional or live intravital imaging has uncovered novel insights into biological mechanisms or modes of drug action. Furthermore, we offer a prospective view of how imaging applications may be integrated further with the aim of understanding disease in a more physiological and functional manner within the framework of the drug discovery process. Intravital imaging offers a new approach to study disease in living tissue with greater fidelity and biological complexity than can be achieved in many 2D-settings. Here we highlight how 3D or live intravital imaging has uncovered biological mechanisms or modes of drug action and we offer a view of how this may be integrated into the early drug discovery process. © 2013 FEBS.