Targeting the PI3K/AKT/mTOR Signaling Pathway in Glioblastoma: Novel Therapeutic Agents and Advances in Understanding

Overview

Journal Tumour Biol

Publisher Sage Publications

Specialty Oncology

Date 2013 Apr 30

PMID 23625692

Citations 72

Authors

Arshawn Sami

Michael Karsy

Affiliations

Soon will be listed here.

Abstract

Glioblastoma multiforme (GBM) is a grade IV astrocytoma with a median survival of 12 months despite current multi-modal treatment options. GBM is distinguished clinicopathologically into primary and secondary subtypes. Mutations of phosphatase and tensin homolog, and subsequent upregulation of the downstream protein kinase B/mammalian target of rapamycin (mTOR) signaling pathway, are commonly seen in primary GBM and less predominantly in secondary GBM. While investigations into targeted treatments of mTOR have been attempted, feedback regulation within the mTOR signaling pathway may account for therapeutic resistance. Currently, rapamycin analogs, dual-targeted mTOR complex 1 and 2 agents as well as dual mTOR and phosphatidylinositol-3 kinase-targeted agents are being investigated experimentally and in clinical trials. This review will discuss the experimental potential of these agents in the treatment of GBM and their current stage in the GBM drug pipeline. Knowledge obtained from the application of these agents can help in understanding the pathogenesis of GBM as well as delineating subsequent treatment strategies.

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