A critical evaluation of PI3K inhibition in Glioblastoma and Neuroblastoma therapy
DOI:
https://doi.org/10.13052/2052-8426-2-32Keywords:
PI3K, Glioblastoma, Neuroblastoma, Cancer, Pharmacological inhibitors, Signaling cascadeAbstract
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.
