title: In silico prescription of anticancer drugs to cohorts of 28 tumor types reveals targeting opportunities.
abstract: Large efforts dedicated to detect somatic alterations across tumor genomes/exomes are expected to produce significant improvements in precision cancer medicine. However, high inter-tumor heterogeneity is a major obstacle to developing and applying therapeutic targeted agents to treat most cancer patients. Here, we offer a comprehensive assessment of the scope of targeted therapeutic agents in a large pan-cancer cohort. We developed an in silico prescription strategy based on identification of the driver alterations in each tumor and their druggability options. Although relatively few tumors are tractable by approved agents following clinical guidelines (5.9%), up to 40.2% could benefit from different repurposing options, and up to 73.3% considering treatments currently under clinical investigation. We also identified 80 therapeutically targetable cancer genes.
authors.affiliation: Biomedical Genomics Lab, Research Program on Biomedical Informatics, IMIM Hospital del Mar Medical Research Institute and Universitat Pompeu Fabra, Doctor Aiguader 88, 08003 Barcelona, Catalonia, Spain.
authors.forename: Carlota
authors.initials: C
authors.lastname: Rubio-Perez
authors.affiliation: Biomedical Genomics Lab, Research Program on Biomedical Informatics, IMIM Hospital del Mar Medical Research Institute and Universitat Pompeu Fabra, Doctor Aiguader 88, 08003 Barcelona, Catalonia, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Tamborero
authors.affiliation: Biomedical Genomics Lab, Research Program on Biomedical Informatics, IMIM Hospital del Mar Medical Research Institute and Universitat Pompeu Fabra, Doctor Aiguader 88, 08003 Barcelona, Catalonia, Spain.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Schroeder
authors.affiliation: Systems Pharmacology, Research Program on Biomedical Informatics, IMIM Hospital del Mar Medical Research Institute and Universitat Pompeu Fabra, Doctor Aiguader 88, 08003 Barcelona, Catalonia, Spain.
authors.forename: Albert A
authors.initials: AA
authors.lastname: Antolín
authors.affiliation: Biomedical Genomics Lab, Research Program on Biomedical Informatics, IMIM Hospital del Mar Medical Research Institute and Universitat Pompeu Fabra, Doctor Aiguader 88, 08003 Barcelona, Catalonia, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Deu-Pons
authors.affiliation: Biomedical Genomics Lab, Research Program on Biomedical Informatics, IMIM Hospital del Mar Medical Research Institute and Universitat Pompeu Fabra, Doctor Aiguader 88, 08003 Barcelona, Catalonia, Spain.
authors.forename: Christian
authors.initials: C
authors.lastname: Perez-Llamas
authors.affiliation: Systems Pharmacology, Research Program on Biomedical Informatics, IMIM Hospital del Mar Medical Research Institute and Universitat Pompeu Fabra, Doctor Aiguader 88, 08003 Barcelona, Catalonia, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Mestres
authors.affiliation: Biomedical Genomics Lab, Research Program on Biomedical Informatics, IMIM Hospital del Mar Medical Research Institute and Universitat Pompeu Fabra, Doctor Aiguader 88, 08003 Barcelona, Catalonia, Spain.
authors.forename: Abel
authors.initials: A
authors.lastname: Gonzalez-Perez
authors.affiliation: Biomedical Genomics Lab, Research Program on Biomedical Informatics, IMIM Hospital del Mar Medical Research Institute and Universitat Pompeu Fabra, Doctor Aiguader 88, 08003 Barcelona, Catalonia, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Passeig Lluís Companys 23, 08010 Barcelona, Spain. Electronic address: nuria.lopez@upf.edu.
authors.forename: Nuria
authors.initials: N
authors.lastname: Lopez-Bigas
mesh_terms: D000970:Antineoplastic Agents; D063646:Carcinogenesis / Q000235:genetics*; D002985:Clinical Protocols; D002986:Clinical Trials as Topic; D015331:Cohort Studies; D019295:Computational Biology; D004252:DNA Mutational Analysis; D003658:Decision Making, Computer-Assisted; D058492:Drug Repositioning; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics*; D057285:Precision Medicine / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents