Title:Targeting the PI3K/AKT/mTOR Signaling Pathway in Medulloblastoma
Volume: 15
Issue: 1
Author(s): V. Dimitrova and A. Arcaro
Affiliation:
Keywords:
AKT, clinical trial, medulloblastoma, mTOR, phosphoinositide 3-kinase, PTEN.
Abstract: Medulloblastoma is the most common malignant childhood brain tumor and
is associated with a poor outcome. There is an urgent need to develop novel targeted
therapeutic approaches for medulloblastoma, which will arise from an enhanced
understanding of the disease at the molecular level. Medulloblastoma has been
recognized to be a heterogeneous disease, and no recurrent cancer gene mutations
have been found, although many of the mutations described so far affect key
intracellular signaling pathways, such as sonic hedgehog (SHH) and Wnt/β-catenin.
The PI3K/AKT/mTOR (PAM) signaling pathway controls key cellular responses, such
as cell growth and proliferation, survival, migration and metabolism. Over the last
decades, it has been recognized that this intracellular signaling pathway is frequently
activated by genetic and epigenetic alterations in malignant brain tumors, including
medulloblastoma. Clinical trials have started to evaluate the safety and efficacy of agents targeting this
pathway in malignant brain tumors. Due to the complexity of the PAM signaling pathway, there remain
significant difficulties in the development of novel therapeutic approaches. The future challenges in developing
effective treatments for cancer patients include the development of predictive biomarkers and combinatorial
approaches to effectively target multiple signal transduction pathways. In this review article, we will summarize
the current knowledge about the role of PAM signaling in medulloblastoma and discuss the strategies that are
currently being evaluated with targeted agents against this pathway.
