Journal
ONCOTARGET
Volume 6, Issue 36, Pages 38854-38865Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.5749
Keywords
cancer; targeted therapy; Hippo pathway; small molecules; pharmacogenomics
Categories
Funding
- Associazione Italiana per la Ricerca sul Cancro (AIRC) and AIRC Special Program Molecular Clinical Oncology '5 per mille'
- Italian Ministry of Education, University and Research (COFIN, FIRB-accordi di programma) [RBAP10XKNC_003]
- JDRF foundation [17-2013-326]
- MIUR EPIGEN - Italian Flagship Project Epigenomics [MIUR FIRB RBAP11T3WB]
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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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