title: A critical evaluation of PI3K inhibition in Glioblastoma and Neuroblastoma therapy.
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.
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
authors.forename: Mike-Andrew
authors.initials: MA
authors.lastname: Westhoff
authors.affiliation: Department of Neurosurgery, University Medical Center Ulm, Ulm, Germany ; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY USA.
authors.forename: Georg
authors.initials: G
authors.lastname: Karpel-Massler
authors.affiliation: Laboratorio Analisi Sicilia Catania, Lentini, SR Italy.
authors.forename: Oliver
authors.initials: O
authors.lastname: Brühl
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Enzenmüller
authors.affiliation: Laboratorio Analisi Sicilia Catania, Lentini, SR Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: La Ferla-Brühl
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY USA.
authors.forename: Markus D
authors.initials: MD
authors.lastname: Siegelin
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Nonnenmacher
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
authors.forename: Klaus-Michael
authors.initials: KM
authors.lastname: Debatin
keywords: Cancer; Glioblastoma; Neuroblastoma; PI3K; Pharmacological inhibitors; Signaling cascade