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Topic: Brain tumor cell invasion and metastasis: anatomical, biological and clinical considerations

The role of the PI3K/AKT/mTOR pathway in brain tumor metastasis

Silvia Crespo*, Marcus Kind*, Alexandre Arcaro
Division of Pediatric Hematology/Oncology, Bern University Hospital, CH-3008 Bern, Switzerland.
Correspondence to: Dr. Alexandre Arcaro, Division of Pediatric Hematology/Oncology, Bern University Hospital, Murtenstrasse 35, CH-3008
Bern, Switzerland. E-mail: alexandre.arcaro@dkf.unibe.ch
*Contributed equally to the work.

Alexandre Arcaro is a group leader at Bern University Hospital. He graduated at the University of Lausanne
and obtained a Ph.D. from the University of Fribourg. He was then a postdoc at the Ludwig Institute for Cancer
Research, UCL and Lausanne Branch. He was then a lecturer at Imperial College London. Subsequently, he was
a group leader at the University Children’s Hospital Zurich.

A B S T R AC T
The PI3K/AKT/mTOR (PAM) pathway is involved in a variety of cellular functions and often contributes to oncogenesis and
cancer progression. It has been recognized that this pathway is frequently activated in the most common central nervous system
cancers of adults and children, malignant gliomas and medulloblastomas (MB). In these tumors, the PAM network controls key
functions necessary for cell invasion and metastasis, such as cell motility. This review summarizes the current knowledge about
the role of PAM signaling in cell invasion and metastasis in gliomas and MB. Current approaches to inhibit cell invasion and
metastasis by targeting the PAM pathway will also be discussed.

Key words: PI3K/AKT/mTOR pathway; glioblastoma; medulloblastoma; metastasis

INTRODUCTION Medulloblastomas are embryonal tumors that originate
from fetal tissue due to aberrant developmental signaling.
[3]
Tumors of the central nervous system include a broad range By using treatment protocols that combine chemotherapy,
of neoplasms that arise from different cell lineages. The surgery and cranio-spinal radiotherapy, 70-80% of patients
most common variants in adult and pediatric populations can be cured, albeit with debilitating long term side effects. [4]
are malignant gliomas and MB, respectively.
Advances in molecular biology have led to remarkable
Glioblastoma (GBM) is a highly aggressive tumor that insights into the understanding of the underlying molecular
arises from different glial cell types. Based on WHO pathogenesis of malignant gliomas and MB and have
classification, GBM is a grade IV astrocytoma that either
develops de novo (primary GBM) or gradually from lower revealed specific pathways and signaling networks that
[5,6]
grade astrocytomas (secondary GBM). Due to limited promote tumorigenesis in these malignancies. These
[1]
therapy options, the median survival is a dismal 15 months frequently feature aberrant receptor tyrosine kinase (RTK)
with standard of care, which includes surgical resection, signaling via the PI3K/AKT/mTOR (PAM) pathway.
temozolomide chemotherapy and radiation. [2]
This is an open access article distributed under the terms of the Creative
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Website: For reprints contact: service@oaepublish.com
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How to cite this article: Crespo S, Kind M, Arcaro A. The role of
the PI3K/AKT/mTOR pathway in brain tumor metastasis. J Cancer
DOI: Metastasis Treat 2016;2:80-9.
10.20517/2394-4722.2015.72
Received: 29-09-2015; Accepted: 30-11-2015.

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©2016 Journal of Cancer Metastasis and Treatment ¦ Published by OAE Publishing Inc.