Blocking epithelial-to-mesenchymal transition in glioblastoma with a sextet of repurposed drugs: the EIS regimen
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Richard E. Kast1, Nicolas Skuli2, Georg Karpel-Massler3, Guido Frosina4, Timothy Ryken5 and Marc-Eric Halatsch3
1 IIAIGC Study Center, Burlington, VT, USA
2 INSERM, Centre de Recherches en Cancérologie de Toulouse, CRCT, Inserm/Université Toulouse III, Paul Sabatier, Hubert Curien, Toulouse, France
3 Department of Neurosurgery, Ulm University Hospital, Albert-Einstein-Allee, Ulm, Germany
4 Mutagenesis & Cancer Prevention Unit, IRCCS Azienda Ospedaliera Universitaria San Martino, IST Istituto Nazionale per la Ricerca sul Cancro, Largo Rosanna Benzi, Genoa, Italy
5 Department of Neurosurgery, University of Kansas, Lawrence, KS, USA
Richard E. Kast, email:
Keywords: AMPK, EIS regimen, EMT, glioma, glioblastoma
Received: March 02, 2017 Accepted: May 12, 2017 Published: June 01, 2017
This paper outlines a treatment protocol to run alongside of standard current treatment of glioblastoma- resection, temozolomide and radiation. The epithelial to mesenchymal transition (EMT) inhibiting sextet, EIS Regimen, uses the ancillary attributes of six older medicines to impede EMT during glioblastoma. EMT is an actively motile, therapy-resisting, low proliferation, transient state that is an integral feature of cancers’ lethality generally and of glioblastoma specifically. It is believed to be during the EMT state that glioblastoma’s centrifugal migration occurs. EMT is also a feature of untreated glioblastoma but is enhanced by chemotherapy, by radiation and by surgical trauma. EIS Regimen uses the antifungal drug itraconazole to block Hedgehog signaling, the antidiabetes drug metformin to block AMP kinase (AMPK), the analgesic drug naproxen to block Rac1, the anti-fibrosis drug pirfenidone to block transforming growth factor-beta (TGF-beta), the psychiatric drug quetiapine to block receptor activator NFkB ligand (RANKL) and the antibiotic rifampin to block Wnt- all by their previously established ancillary attributes. All these systems have been identified as triggers of EMT and worthy targets to inhibit. The EIS Regimen drugs have a good safety profile when used individually. They are not expected to have any new side effects when combined. Further studies of the EIS Regimen are needed.
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