Emerging targets for glioblastoma stem cell therapy

Ahmad Safa, Mohammad Reza Saadatzadeh, Aaron Cohen-Gadol, Karen Pollok, Khadijeh Bijangi-Vishehsaraei

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Glioblastoma multiforme (GBM), designated as World Health Organization (WHO) grade IV astrocytoma, is a lethal and therapy-resistant brain cancer comprised of several tumor cell subpopulations, including GBM stem cells (GSCs) which are believed to contribute to tumor recurrence following initial response to therapies. Emerging evidence demonstrates that GBM tumors are initiated from GSCs. The development and use of novel therapies including small molecule inhibitors of specific proteins in signaling pathways that regulate stemness, proliferation and migration of GSCs, immunotherapy, and non-coding microRNAs may provide better means of treating GBM. Identification and characterization of GSC-specific signaling pathways would be necessary to identify specific therapeutic targets which may lead to the development of more efficient therapies selectively targeting GSCs. Several signaling pathways including mTOR, AKT, maternal embryonic leucine zipper kinase (MELK), NOTCH1 and Wnt/β-catenin as well as expression of cancer stem cell markers CD133, CD44, Oct4, Sox2, Nanog, and ALDH1A1 maintain GSC properties. Moreover, the data published in the Cancer Genome Atlas (TCGA) specifically demonstrated the activated PI3K/AKT/mTOR pathway in GBM tumorigenesis. Studying such pathways may help to understand GSC biology and lead to the development of potential therapeutic interventions to render them more sensitive to chemotherapy and radiation therapy. Furthemore, recent demonstration of dedifferentiation of GBM cell lines into CSC-like cells prove that any successful therapeutic agent or combination of drugs for GBM therapy must eliminate not only GSCs, but the differentiated GBM cells and the entire bulk of tumor cells.

Original languageEnglish (US)
Pages (from-to)19-31
Number of pages13
JournalJournal of Biomedical Research
Volume30
Issue number1
DOIs
StatePublished - 2016

Fingerprint

Glioblastoma
Cell- and Tissue-Based Therapy
Stem cells
Stem Cells
Tumors
Cells
Therapeutics
Neoplasms
Cytology
Catenins
Leucine Zippers
Chemotherapy
Neoplastic Stem Cells
Atlases
Radiotherapy
Drug Combinations
MicroRNAs
Phosphatidylinositol 3-Kinases
Brain Neoplasms
Immunotherapy

Keywords

  • ALDH1A1
  • CD133
  • CD44
  • Dedifferentiation
  • Glioblastoma multiforme
  • SOX2
  • Stem cells

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Emerging targets for glioblastoma stem cell therapy. / Safa, Ahmad; Saadatzadeh, Mohammad Reza; Cohen-Gadol, Aaron; Pollok, Karen; Bijangi-Vishehsaraei, Khadijeh.

In: Journal of Biomedical Research, Vol. 30, No. 1, 2016, p. 19-31.

Research output: Contribution to journalArticle

Safa, Ahmad ; Saadatzadeh, Mohammad Reza ; Cohen-Gadol, Aaron ; Pollok, Karen ; Bijangi-Vishehsaraei, Khadijeh. / Emerging targets for glioblastoma stem cell therapy. In: Journal of Biomedical Research. 2016 ; Vol. 30, No. 1. pp. 19-31.
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