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
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Cristian Taccioli1,*, Giovanni Sorrentino2,3,*, Alessandro Zannini2,3, Jimmy Caroli1, Domenico Beneventano4, Laura Anderlucci5, Marco Lolli6, Silvio Bicciato1, Giannino Del Sal2,3
1Department of Life Sciences, University of Modena and Reggio Emilia, Modena 41125, Italy
2Laboratorio Nazionale CIB (LNCIB), Area Science Park, Trieste 34149, Italy
3Dipartimento di Scienze della Vita, Università degli Studi di Trieste, Trieste 34149, Italy
4Dipartimento di Ingegneria “Enzo Ferrari”, Modena 41125, Italy
5Dipartimento di Scienze Statistiche, Bologna 40124, Italy
6Department of Science and Drug Technology, University of Torino, Torino 10125, Italy
*These authors have contributed equally to this work
Silvio Bicciato, e-mail: [email protected]
Giannino Del Sal, e-mail: [email protected]
Keywords: cancer, targeted therapy, Hippo pathway, small molecules, pharmacogenomics
Received: August 10, 2015 Accepted: October 05, 2015 Published: October 15, 2015
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.
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