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Dell'Anno I, Martin SA, Barbarino M, et al. Drug-repositioning screening identified fludarabine and risedronic acid as potential therapeutic compounds for malignant pleural mesothelioma. Invest New Drugs. 2020;39(3):644-657doi: 10.1007/s10637-020-01040-y.
Dell'Anno, I., Martin, S. A., Barbarino, M., Melani, A., Silvestri, R., Bottaro, M., Paolicchi, E., Corrado, A., Cipollini, M., Melaiu, O., Giordano, A., Luzzi, L., Gemignani, F., & Landi, S. (2021). Drug-repositioning screening identified fludarabine and risedronic acid as potential therapeutic compounds for malignant pleural mesothelioma. Investigational new drugs, 39(3), 644-657. https://doi.org/10.1007/s10637-020-01040-y
Dell'Anno, Irene, et al. "Drug-repositioning screening identified fludarabine and risedronic acid as potential therapeutic compounds for malignant pleural mesothelioma." Investigational new drugs vol. 39,3 (2021): 644-657. doi: https://doi.org/10.1007/s10637-020-01040-y
Dell'Anno I, Martin SA, Barbarino M, Melani A, Silvestri R, Bottaro M, Paolicchi E, Corrado A, Cipollini M, Melaiu O, Giordano A, Luzzi L, Gemignani F, Landi S. Drug-repositioning screening identified fludarabine and risedronic acid as potential therapeutic compounds for malignant pleural mesothelioma. Invest New Drugs. 2021 Jun;39(3):644-657. doi: 10.1007/s10637-020-01040-y. Epub 2020 Dec 09. PMID: 33300108; PMCID: PMC8068714.
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Invest New Drugs. 2021 Jun;39(3):644-657. doi: 10.1007/s10637-020-01040-y. Epub 2020 Dec 09.

Drug-repositioning screening identified fludarabine and risedronic acid as potential therapeutic compounds for malignant pleural mesothelioma.

Investigational new drugs

Irene Dell'Anno, Sarah A Martin, Marcella Barbarino, Alessandra Melani, Roberto Silvestri, Maria Bottaro, Elisa Paolicchi, Alda Corrado, Monica Cipollini, Ombretta Melaiu, Antonio Giordano, Luca Luzzi, Federica Gemignani, Stefano Landi

Affiliations

  1. Department of Biology, Genetic Unit, University of Pisa, 56126, Pisa, Italy.
  2. Centre for Cancer Cell and Molecular Biology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK.
  3. Department of Medical Biotechnologies, University of Siena, 53100, Siena, Italy.
  4. Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, 19122, USA.
  5. Immuno-Oncology Laboratory, Department of Paediatric Haematology/Oncology and of Cell and Gene Therapy, Ospedale Pediatrico Bambino Gesù, IRCCS, 00165, Rome, Italy.
  6. Department of Medicine, Surgery and Neurosciences, Siena University Hospital, 53100, Siena, Italy.
  7. Department of Biology, Genetic Unit, University of Pisa, 56126, Pisa, Italy. [email protected].

PMID: 33300108 PMCID: PMC8068714 DOI: 10.1007/s10637-020-01040-y

Abstract

Objectives Malignant pleural mesothelioma (MPM) is an occupational disease mainly due to asbestos exposure. Effective therapies for MPM are lacking, making this tumour type a fatal disease. Materials and Methods In order to meet this need and in view of a future "drug repositioning" 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. Results 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). Conclusion 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.

Keywords: Antimetabolite; Bisphosphonate; Drug repositioning; Fludarabine; Mesothelioma; Risedronic acid

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