title: Combining imaging and pathway profiling: an alternative approach to cancer drug discovery.
abstract: Conventional drug discovery strategies are typically 'target centric' based on the selection of lead compounds with optimised 'on-target' potency and selectivity profiles. However, high-attrition rates are often the result of compensatory or redundant cancer mechanisms and the fact that tumours do not find it difficult to escape inhibition of a single pathway. In this article, we highlight two emerging and complimentary technologies; namely phenotypic imaging and post-translational pathway profiling, which when combined with relevant disease models can provide pharmacodiagnostic and drug combination strategies that predict and counteract inherent and adaptive drug resistance. The implementation of such approaches at early stages of the drug discovery process enables more informed decisions on candidate drug selection and how to maximise and predict efficacy before clinical development.
authors.affiliation: Edinburgh Cancer Research UK Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, UK. N.Carragher@ed.ac.uk
authors.forename: Neil O
authors.initials: NO
authors.lastname: Carragher
authors.forename: Valerie G
authors.initials: VG
authors.lastname: Brunton
authors.forename: Margaret C
authors.initials: MC
authors.lastname: Frame
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003952:Diagnostic Imaging / Q000379:methods*; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents