A conceptually new treatment approach for relapsed glioblastoma: Coordinated undermining of survival paths with nine repurposed drugs (CUSP9) by the International Initiative for Accelerated Improvement of Glioblastoma Care

Richard E. Kast*, John A. Boockvar, Ansgar Brüning, Francesco Cappello, Wen Wei Chang, Boris Cvek, Q. Ping Dou, Alfonso Duenas-Gonzalez, Thomas Efferth, Daniele Focosi, Seyed H. Ghaffari, Georg Karpel-Massler, Kirsi Ketola, Alireza Khoshnevisan, Daniel Keizman, Nicolas Magné, Christine Marosi, Kerrie McDonald, Miguel Muñoz, Ameya ParanjpeMohammad H. Pourgholami, Iacopo Sardi, Avishay Sella, Kalkunte S. Srivenugopal, Marco Tuccori, Weiguang Wang, Christian R. Wirtz, Marc Eric Halatsch

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

To improve prognosis in recurrent glioblastoma we developed a treatment protocol based on a combination of drugs not traditionally thought of as cytotoxic chemotherapy agents but that have a robust history of being well-tolerated and are already marketed and used for other non-cancer indications. Focus was on adding drugs which met these criteria: a) were pharmacologically well characterized, b) had low likelihood of adding to patient side effect burden, c) had evidence for interfering with a recognized, well-characterized growth promoting element of glioblastoma, and d) were coordinated, as an ensemble had reasonable likelihood of concerted activity against key biological features of glioblastoma growth. We found nine drugs meeting these criteria and propose adding them to continuous low dose temozolomide, a currently accepted treatment for relapsed glioblastoma, in patients with recurrent disease after primary treatment with the Stupp Protocol. The nine adjuvant drug regimen, Coordinated Undermining of Survival Paths, CUSP9, then are aprepitant, artesunate, auranofin, captopril, copper gluconate, disulfiram, ketoconazole, nelfinavir, sertraline, to be added to continuous low dose temozolomide. We discuss each drug in turn and the specific rationale for use- how each drug is expected to retard glioblastoma growth and undermine glioblastoma's compensatory mechanisms engaged during temozolomide treatment. The risks of pharmacological interactions and why we believe this drug mix will increase both quality of life and overall survival are reviewed.

Original languageEnglish
Pages (from-to)502-530
Number of pages29
JournalOncotarget
Volume4
Issue number4
DOIs
StatePublished - Apr 2013
Externally publishedYes

Keywords

  • Angiotensin
  • Aprepitant
  • Artesunate
  • Auranofin
  • Captopril
  • Cytokines
  • Disulfiram
  • Glioblastoma
  • Ketoconazole
  • Nelfinavir
  • Neurokinin
  • Sertraline
  • Temozolomide

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