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Effective therapies for MPM are lacking, making this tumour type a fatal disease. <jats:italic>Materials and Methods<\/jats:italic> In order to meet this need and in view of a future \u201cdrug repositioning\u201d approach, here we screened five MPM (Mero-14, Mero-25, IST-Mes2, NCI-H28 and MSTO-211H) and one SV40-immortalized mesothelial cell line (MeT-5A) as a non-malignant model, with a library of 1170 FDA-approved drugs. <jats:italic>Results<\/jats:italic> Among several potential compounds, we found that fludarabine (F-araA) and, to a lesser extent, risedronic acid (RIS) were cytotoxic in MPM cells, in comparison to the non-malignant Met-5A cells. In particular, F-araA reduced the proliferation and the colony formation ability of the MPM malignant cells, in comparison to the non-malignant control cells, as demonstrated by proliferation and colony formation assays, in addition to measurement of the phospho-ERK\/total-ERK ratio. We have shown that the response to F-araA was not dependent upon the expression of DCK and NT5E enzymes, nor upon their functional polymorphisms (rs11544786 and rs2295890, respectively). <jats:italic>Conclusion<\/jats:italic> This drug repositioning screening approach has identified that F-araA could be therapeutically active against MPM cells, in addition to other tumour types, by inhibiting STAT1 expression and nucleic acids synthesis. Further experiments are required to fully investigate this.<\/jats:p>","DOI":"10.1007\/s10637-020-01040-y","type":"journal-article","created":{"date-parts":[[2020,12,9]],"date-time":"2020-12-09T22:12:08Z","timestamp":1607551928000},"page":"644-657","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Drug-repositioning screening identified fludarabine and risedronic acid as potential therapeutic compounds for malignant pleural mesothelioma"],"prefix":"10.1007","volume":"39","author":[{"given":"Irene","family":"Dell\u2019Anno","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah A.","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcella","family":"Barbarino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Melani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Silvestri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Bottaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Paolicchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alda","family":"Corrado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Cipollini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ombretta","family":"Melaiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Giordano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Luzzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Gemignani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Landi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,12,9]]},"reference":[{"issue":"7776","key":"1040_CR1","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1038\/s41586-019-1600-x","volume":"574","author":"DL van der Velden","year":"2019","unstructured":"van der Velden DL, Hoes LR, van der Wijngaart H, van Berge Henegouwen JM, van Werkhoven E, Roepman P, Schilsky RL, de Leng WWJ, Huitema ADR, Nuijen B, Nederlof PM, van Herpen CML, de Groot DJA, Devriese LA, Hoeben A, de Jonge MJA, Chalabi M, Smit EF, de Langen AJ, Mehra N, Labots M, Kapiteijn E, Sleijfer S, Cuppen E, Verheul HMW, Gelderblom H, Voest EE (2019) The drug rediscovery protocol facilitates the expanded use of existing anticancer drugs. 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Sarah A. Martin declares that she has no conflict of interest. Marcella Barbarino declares that she has no conflict of interest. Alessandra Melani declares that she has no conflict of interest. Roberto Silvestri declares that he has no conflict of interest. Maria Bottaro declares that she has no conflict of interest. Elisa Paolicchi declares that she has no conflict of interest. Alda Corrado declares that he has no conflict of interest. Monica Cipollini declares that she has no conflict of interest. Ombretta Melaiu declares that she has no conflict of interest. Antonio Giordano declares that he has no conflict of interest. Luca Luzzi declares that he has no conflict of interest. Federica Gemignani declares that she has no conflict of interest. Stefano Landi declares that he has no conflict of interest.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Disclosure of potential conflicts of interest"}},{"value":"This article does not contain any studies with human participants or animals performed by any of the authors.","order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Research involving human participants and\/or animals"}},{"value":"For this type of study, formal consent is not required.","order":9,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}