title: 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.
authors.affiliation: The Beatson Institute for Cancer Research, Glasgow, UK.
authors.forename: Max
authors.initials: M
authors.lastname: Nobis
authors.forename: Neil O
authors.initials: NO
authors.lastname: Carragher
authors.forename: Ewan J
authors.initials: EJ
authors.lastname: McGhee
authors.forename: Jennifer P
authors.initials: JP
authors.lastname: Morton
authors.forename: Owen J
authors.initials: OJ
authors.lastname: Sansom
authors.forename: Kurt I
authors.initials: KI
authors.lastname: Anderson
authors.forename: Paul
authors.initials: P
authors.lastname: Timpson
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003952:Diagnostic Imaging; D055808:Drug Discovery; D006801:Humans; D008856:Microscopy, Fluorescence; D009369:Neoplasms / Q000175:diagnosis* / Q000188:drug therapy; D015398:Signal Transduction / Q000187:drug effects*; D059016:Tumor Microenvironment / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents
keywords: adhesions; biosensors; drug discovery; fluorescence lifetime imaging microscopy; fluorescence recovery after photobleaching; fluorescence resonance energy transfer; intravital imaging; invasion; metastasis; optical windows