title: Chemical biology approaches to target validation in cancer.
abstract: Target validation is a crucial element of drug discovery. Especially given the wealth of potential targets emerging from cancer genome sequencing and functional genetic screens, and also considering the time and cost of downstream drug discovery efforts, it is essential to build confidence in a proposed target, ideally using different technical approaches. We argue that complementary biological and chemical biology strategies are essential for robust target validation. We discuss recent progress in the discovery and application of high quality chemical tools and other chemical biology approaches to target validation in cancer. Among other topical examples, we highlight the emergence of designed irreversible chemical tools to study potential target proteins and oncogenic pathways that were hitherto regarded as poorly druggable.
authors.affiliation: Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London, UK. Electronic address: julian.blagg@icr.ac.uk.
authors.forename: Julian
authors.initials: J
authors.lastname: Blagg
authors.affiliation: Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London, UK. Electronic address: paul.workman@icr.ac.uk.
authors.forename: Paul
authors.initials: P
authors.lastname: Workman
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D055808:Drug Discovery / Q000379:methods*; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D060066:Protein Interaction Maps; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D057170:Translational Research, Biomedical
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors