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Antitumor action of temozolomide, ritonavir and aprepitant against human glioma cells

  • Laboratory Investigation
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Abstract

In the effort to find better treatments for glioblastoma we tested several currently marketed non-chemotherapy drugs for their ability to enhance the standard cytotoxic drug currently used to treat glioblastoma- temozolomide. We tested four antiviral drugs- acyclovir, cidofovir, maraviroc, ritonavir, and an anti-emetic, aprepitant. We found no cytotoxicity of cidofovir and discussed possible reasons for discrepancy from previous findings of others. We also found no cytotoxicity from acyclovir or maraviroc also in contradistinction to predictions. Cytotoxicity to glioma cell line GAMG for temozolomide alone was 14 %, aprepitant alone 7 %, ritonavir alone 14 %, while temozolomide + aprepitant was 19 %, temozolomide + ritonavir 34 %, ritonavir + aprepitant 64 %, and all three, temozolomide + ritonavir + aprepitant 78 %. We conclude that a remarkable synergy exists between aprepitant and ritonavir. Given the long clinical experience with these two well-tolerated drugs in treating non-cancer conditions, and the current median survival of glioblastoma of 2 years, a trial is warranted of adding these two simple drugs to current standard treatment with temozolomide.

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Acknowledgments

The authors wish to thank Mr. Javier Muñoz (University of Sevilla, Spain) and Mr. José Manuel Praena-Fernández (Virgen del Rocío University Hospital, Statistical service, Sevilla, Spain) for technical assistance.

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Authors and Affiliations

  1. IIAIGC Headquarters, Dean of Studies, 22 Church St, Burlington, VT, 05401, USA

    Richard E. Kast

  2. Research Laboratory on Neuropeptides (IBIS), Virgen del Rocío University Hospital, Avda. Manuel Siurot s/n, 41013, Seville, Spain

    Susana Ramiro, Sandra Lladó, Salvador Toro & Miguel Muñoz

  3. Laboratory of Neuroanatomy of the Peptidergic Systems (Lab. 14), Institute of Neurosciences of Castilla y León (INCYL), University of Salamanca, Salamanca, Spain

    Rafael Coveñas

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  1. Richard E. Kast
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  2. Susana Ramiro
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  4. Salvador Toro
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  5. Rafael Coveñas
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Correspondence to Richard E. Kast or Miguel Muñoz.

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Conflicts of interest

USPTO Application No. 20090012086 “Use of non-peptide NK-1 receptor antagonists for the production of apoptosis in tumor cells” (Miguel Muñoz).

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Kast, R.E., Ramiro, S., Lladó, S. et al. Antitumor action of temozolomide, ritonavir and aprepitant against human glioma cells. J Neurooncol 126, 425–431 (2016). https://doi.org/10.1007/s11060-015-1996-6

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