title: Objective assessment of cancer genes for drug discovery.
abstract: Selecting the best targets is a key challenge for drug discovery, and achieving this effectively, efficiently and systematically is particularly important for prioritizing candidates from the sizeable lists of potential therapeutic targets that are now emerging from large-scale multi-omics initiatives, such as those in oncology. Here, we describe an objective, systematic, multifaceted computational assessment of biological and chemical space that can be applied to any human gene set to prioritize targets for therapeutic exploration. We use this approach to evaluate an exemplar set of 479 cancer-associated genes, reveal the tension between biological relevance and chemical tractability, and describe major gaps in available knowledge that could be addressed to aid objective decision-making. We also propose drug repurposing opportunities and identify potentially druggable cancer-associated proteins that have been poorly explored with regard to the discovery of small-molecule modulators, despite their biological relevance.
authors.affiliation: Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London, UK.
authors.forename: Mishal N
authors.initials: MN
authors.lastname: Patel
authors.forename: Mark D
authors.initials: MD
authors.lastname: Halling-Brown
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Tym
authors.forename: Paul
authors.initials: P
authors.lastname: Workman
authors.forename: Bissan
authors.initials: B
authors.lastname: Al-Lazikani
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D003657:Decision Making; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents