{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:49:54Z","timestamp":1791910194771,"version":"4.3.4"},"reference-count":60,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,4,18]],"date-time":"2022-04-18T00:00:00Z","timestamp":1650240000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"HPC-EUROPA3","award":["INFRAIA-2016-1-730897"],"award-info":[{"award-number":["INFRAIA-2016-1-730897"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Despite remarkable efforts of computational and predictive pharmacology to improve therapeutic strategies for complex diseases, only in a few cases have the predictions been eventually employed in the clinics. One of the reasons behind this drawback is that current predictive approaches are based only on the integration of molecular perturbation of a certain disease with drug sensitivity signatures, neglecting intrinsic properties of the drugs. Here we integrate mechanistic and chemocentric approaches to drug repositioning by developing an innovative network pharmacology strategy. We developed a multilayer network-based computational framework integrating perturbational signatures of the disease as well as intrinsic characteristics of the drugs, such as their mechanism of action and chemical structure. We present five case studies carried out on public data from The Cancer Genome Atlas, including invasive breast cancer, colon adenocarcinoma, lung squamous cell carcinoma, hepatocellular carcinoma and prostate adenocarcinoma. Our results highlight paclitaxel as a suitable drug for combination therapy for many of the considered cancer types. In addition, several non-cancer-related genes representing unusual drug targets were identified as potential candidates for pharmacological treatment of cancer.<\/jats:p>","DOI":"10.3390\/cancers14082043","type":"journal-article","created":{"date-parts":[[2022,4,18]],"date-time":"2022-04-18T22:04:02Z","timestamp":1650319442000},"page":"2043","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Integrated Network Pharmacology Approach for Drug Combination Discovery: A Multi-Cancer Case Study"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2554-9879","authenticated-orcid":false,"given":"Antonio","family":"Federico","sequence":"first","affiliation":[{"name":"Finnish Hub for Development and Validation of Integrated Approaches (FHAIVE), Tampere University, 33100 Tampere, Finland"},{"name":"Faculty of Medicine and Health Technology, Tampere University, 33100 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3997-2339","authenticated-orcid":false,"given":"Michele","family":"Fratello","sequence":"additional","affiliation":[{"name":"Finnish Hub for Development and Validation of Integrated Approaches (FHAIVE), Tampere University, 33100 Tampere, Finland"},{"name":"Faculty of Medicine and Health Technology, Tampere University, 33100 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Scala","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Naples \u201cFederico II\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"M\u00f6bus","sequence":"additional","affiliation":[{"name":"Finnish Hub for Development and Validation of Integrated Approaches (FHAIVE), Tampere University, 33100 Tampere, Finland"},{"name":"Faculty of Medicine and Health Technology, Tampere University, 33100 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisa","family":"Pavel","sequence":"additional","affiliation":[{"name":"Finnish Hub for Development and Validation of Integrated Approaches (FHAIVE), Tampere University, 33100 Tampere, Finland"},{"name":"Faculty of Medicine and Health Technology, Tampere University, 33100 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0999-4796","authenticated-orcid":false,"given":"Giusy","family":"del Giudice","sequence":"additional","affiliation":[{"name":"Finnish Hub for Development and Validation of Integrated Approaches (FHAIVE), Tampere University, 33100 Tampere, Finland"},{"name":"Faculty of Medicine and Health Technology, Tampere University, 33100 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Ceccarelli","sequence":"additional","affiliation":[{"name":"Department of Electrical Engineering and Information Technology (DIETI), University of Naples \u201cFederico II\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7294-6933","authenticated-orcid":false,"given":"Valerio","family":"Costa","sequence":"additional","affiliation":[{"name":"Institute of Genetics and Biophysics \u201cAdriano Buzzati-Traverso\u201d, CNR, Via P. Castellino 111, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9924-1482","authenticated-orcid":false,"given":"Alfredo","family":"Ciccodicola","sequence":"additional","affiliation":[{"name":"Institute of Genetics and Biophysics \u201cAdriano Buzzati-Traverso\u201d, CNR, Via P. Castellino 111, 80131 Naples, Italy"},{"name":"Department of Science and Technology, University of Naples \u201cParthenope\u201d, 80143 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8693-5285","authenticated-orcid":false,"given":"Vittorio","family":"Fortino","sequence":"additional","affiliation":[{"name":"School of Medicine, Institute of Biomedicine, University of Eastern Finland, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3374-1492","authenticated-orcid":false,"given":"Angela","family":"Serra","sequence":"additional","affiliation":[{"name":"Finnish Hub for Development and Validation of Integrated Approaches (FHAIVE), Tampere University, 33100 Tampere, Finland"},{"name":"Faculty of Medicine and Health Technology, Tampere University, 33100 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9195-9003","authenticated-orcid":false,"given":"Dario","family":"Greco","sequence":"additional","affiliation":[{"name":"Finnish Hub for Development and Validation of Integrated Approaches (FHAIVE), Tampere University, 33100 Tampere, Finland"},{"name":"Faculty of Medicine and Health Technology, Tampere University, 33100 Tampere, Finland"},{"name":"Institute of Biotechnology, University of Helsinki, 00100 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1146\/annurev-pharmtox-010919-023537","article-title":"Using What We Already Have: Uncovering New Drug Repurposing Strategies in Existing Omics Data","volume":"60","author":"Pulley","year":"2020","journal-title":"Annu. 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