title: Advancing cancer drug discovery towards more agile development of targeted combination therapies.
abstract: Current drug-discovery strategies are typically 'target-centric' and are based upon high-throughput screening of large chemical libraries against nominated targets and a selection of lead compounds with optimized 'on-target' potency and selectivity profiles. However, high attrition of targeted agents in clinical development suggest that combinations of targeted agents will be most effective in treating solid tumors if the biological networks that permit cancer cells to subvert monotherapies are identified and retargeted. Conventional drug-discovery and development strategies are suboptimal for the rational design and development of novel drug combinations. In this article, we highlight a series of emerging technologies supporting a less reductionist, more agile, drug-discovery and development approach for the rational design, validation, prioritization and clinical development of novel drug combinations.
authors.affiliation: Edinburgh Cancer Research UK Centre, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh, UK. n.carragher@ed.ac.uk
authors.forename: Neil O
authors.initials: NO
authors.lastname: Carragher
authors.forename: Asier
authors.initials: A
authors.lastname: Unciti-Broceta
authors.forename: David A
authors.initials: DA
authors.lastname: Cameron
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D055808:Drug Discovery; D004359:Drug Therapy, Combination; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents