A critical evaluation of PI3K inhibition in Glioblastoma and Neuroblastoma therapy

  • Mike-Andrew Westhoff Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany
  • Georg Karpel-Massler Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany
  • Oliver Brühl Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany
  • Stefanie Enzenmüller Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany
  • Katia La Ferla-Brühl Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany
  • Markus Siegelin Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany
  • Lisa Nonnenmacher Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany
  • Klause-Michael Debatin Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany
Keywords: PI3K, Glioblastoma, Neuroblastoma, Cancer, Pharmacological inhibitors, Signaling cascade

Abstract

Members of the PI3K/Akt/mTor signaling cascade are among the most frequently altered proteins in cancer, yet the therapeutic application of pharmacological inhibitors of this signaling network, either as monotherapy or in combination therapy (CT) has so far not been particularly successful. In this review we will focus on the role of PI3K/Akt/mTOR in two distinct tumors, Glioblastoma multiforme (GBM), an adult brain tumor which frequently exhibits PTEN inactivation, and Neuroblastoma (NB), a childhood malignancy that affects the central nervous system and does not harbor any classic alterations in PI3K/Akt signaling. We will argue that inhibitors of PI3K/Akt signaling can be components for potentially promising new CTs in both tumor entities, but further understanding of the signal cascade’s complexity is essential for successful implementation of these CTs. Importantly, failure to do this might lead to severe adverse effects, such as treatment failure and enhanced therapy resistance.

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Published
2014-10-27
Section
Review