title: MDP, a database linking drug response data to genomic information, identifies dasatinib and statins as a combinatorial strategy to inhibit YAP/TAZ in cancer cells.
abstract: Targeted anticancer therapies represent the most effective pharmacological strategies in terms of clinical responses. In this context, genetic alteration of several oncogenes represents an optimal predictor of response to targeted therapy. Integration of large-scale molecular and pharmacological data from cancer cell lines promises to be effective in the discovery of new genetic markers of drug sensitivity and of clinically relevant anticancer compounds. To define novel pharmacogenomic dependencies in cancer, we created the Mutations and Drugs Portal (MDP, http://mdp.unimore.it), a web accessible database that combines the cell-based NCI60 screening of more than 50,000 compounds with genomic data extracted from the Cancer Cell Line Encyclopedia and the NCI60 DTP projects. MDP can be queried for drugs active in cancer cell lines carrying mutations in specific cancer genes or for genetic markers associated to sensitivity or resistance to a given compound. As proof of performance, we interrogated MDP to identify both known and novel pharmacogenomics associations and unveiled an unpredicted combination of two FDA-approved compounds, namely statins and Dasatinib, as an effective strategy to potently inhibit YAP/TAZ in cancer cells.
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena 41125, Italy.
authors.forename: Cristian
authors.initials: C
authors.lastname: Taccioli
authors.affiliation: Laboratorio Nazionale CIB (LNCIB), Area Science Park, Trieste 34149, Italy.|Dipartimento di Scienze della Vita, Università degli Studi di Trieste, Trieste 34149, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sorrentino
authors.affiliation: Laboratorio Nazionale CIB (LNCIB), Area Science Park, Trieste 34149, Italy.|Dipartimento di Scienze della Vita, Università degli Studi di Trieste, Trieste 34149, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Zannini
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena 41125, Italy.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Caroli
authors.affiliation: Dipartimento di Ingegneria "Enzo Ferrari", Modena 41125, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Beneventano
authors.affiliation: Dipartimento di Scienze Statistiche, Bologna 40124, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Anderlucci
authors.affiliation: Department of Science and Drug Technology, University of Torino, Torino 10125, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Lolli
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena 41125, Italy.
authors.forename: Silvio
authors.initials: S
authors.lastname: Bicciato
authors.affiliation: Laboratorio Nazionale CIB (LNCIB), Area Science Park, Trieste 34149, Italy.|Dipartimento di Scienze della Vita, Università degli Studi di Trieste, Trieste 34149, Italy.
authors.forename: Giannino
authors.initials: G
authors.lastname: Del Sal
mesh_terms: D000217:Acyltransferases; D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D045744:Cell Line, Tumor; D000069439:Dasatinib / Q000494:pharmacology*; D030541:Databases, Genetic; D062313:Databases, Pharmaceutical; D019073:HT29 Cells; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D010597:Pharmacogenetics / Q000379:methods*; D010750:Phosphoproteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010750:Phosphoproteins; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; D000217:Acyltransferases; C108675:TAFAZZIN protein, human; D000069439:Dasatinib
keywords: Hippo pathway; cancer; pharmacogenomics; small molecules; targeted therapy