Recent advances in the use of PI3K inhibitors for glioblastoma multiforme: Current preclinical and clinical development

Hua fu Zhao, Jing Wang, Wei Shao, Chang peng Wu, Zhong ping Chen, Shing shun Tony To, Wei ping Li

Research output: Journal article publicationReview articleAcademic researchpeer-review

105 Citations (Scopus)

Abstract

Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary tumor in the central nervous system. One of the most widely used chemotherapeutic drugs for GBM is temozolomide, which is a DNA-alkylating agent and its efficacy is dependent on MGMT methylation status. Little progress in improving the prognosis of GBM patients has been made in the past ten years, urging the development of more effective molecular targeted therapies. Hyper-activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway is frequently found in a variety of cancers including GBM, and it plays a central role in the regulation of tumor cell survival, growth, motility, angiogenesis and metabolism. Numerous PI3K inhibitors including pan-PI3K, isoform-selective and dual PI3K/mammalian target of rapamycin (mTOR) inhibitors have exhibited favorable preclinical results and entered clinical trials in a range of hematologic malignancies and solid tumors. Furthermore, combination of inhibitors targeting PI3K and other related pathways may exert synergism on suppressing tumor growth and improving patients' prognosis. Currently, only a handful of PI3K inhibitors are in phase I/II clinical trials for GBM treatment. In this review, we focus on the importance of PI3K/Akt pathway in GBM, and summarize the current development of PI3K inhibitors alone or in combination with other inhibitors for GBM treatment from preclinical to clinical studies.

Original languageEnglish
Article number100
JournalMolecular Cancer
Volume16
Issue number1
DOIs
Publication statusPublished - 7 Jun 2017

Keywords

  • GBM
  • Glioblastoma
  • MTOR
  • PI3K

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research

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