Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2015;15(7):741-52.
doi: 10.1586/14737175.2015.1051968. Epub 2015 May 31.

The role of glioma stem cells in chemotherapy resistance and glioblastoma multiforme recurrence

Brenda Auffinger  1 , Drew Spencer, Peter Pytel, Atique U Ahmed, Maciej S Lesniak
Affiliations
Review

The role of glioma stem cells in chemotherapy resistance and glioblastoma multiforme recurrence

Brenda Auffinger et al. Expert Rev Neurother. 2015.

Abstract

Glioma stem cells (GSCs) constitute a slow-dividing, small population within a heterogeneous glioblastoma. They are able to self-renew, recapitulate a whole tumor, and differentiate into other specific glioblastoma multiforme (GBM) subpopulations. Therefore, they have been held responsible for malignant relapse after primary standard therapy and the poor prognosis of recurrent GBM. The failure of current therapies to eliminate specific GSC subpopulations has been considered a major factor contributing to the inevitable recurrence in GBM patients after treatment. Here, we discuss the molecular mechanisms of chemoresistance of GSCs and the reasons why complete eradication of GSCs is so difficult to achieve. We will also describe the targeted therapies currently available for GSCs and possible mechanisms to overcome such chemoresistance and avoid therapeutic relapse.

Keywords: chemoresistance; glioma stem cells; malignant glioma; mechanisms; plasticity; recurrence.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Histological differences between GBM and low-grade glioma (LGG)
GBM (left) has a central area with densely cellular tumor that exhibits mitoses and endothelial/microvascular proliferation, with infiltration between normal neurons at the periphery of the lesion. (A) Staining for IDH1 and (B) nuclear labeling for p53. LGG (right) H&E staining, with (C) positive IDH1 and (D) positive nuclear p53. Based on the immunoprofile, this particular GBM likely arose as secondary GBM out of a diffuse astrocytoma. 100X magnification.
Figure 2
Figure 2. Origin, self-renewal, and dedifferentiation of GSCs
Image depicting GSGs originating from mutated NSCs (1). Depending on specific environmental cues (2), the “GSC of origin” will undergo either asymmetric or symmetric cell division to give rise to, respectively, self-renewed GSCs and differentiated non-GSCs (3). This will ultimately lead to a genetically and phenotypically heterogeneous GBM. The plastic phenotype is seen by the interconversion between GSCs and non-GSCs (4). Non-mutated neural progenitor cells will originate a wide range of cells in the brain, such as astrocytes, glia cell, and neurons (5).
Figure 3
Figure 3. Representative immunohistochemistry of LGG
LGG (diffuse astrocytoma) (A) H&E staining, (B) positive IDH1 and (C) positive nuclear p53. 200X magnification.
See this image and copyright information in PMC

References

    1. Louis DN, Ohgaki H, Wiestler OD, et al. The 2007 WHO classification of tumours of the central nervous system. Acta neuropathologica. 2007;114(2):97–109. - PMC - PubMed
    1. Legler JM, Ries LA, Smith MA, et al. Cancer surveillance series [corrected]: brain and other central nervous system cancers: recent trends in incidence and mortality. Journal of the National Cancer Institute. 1999;91(16):1382–1390. - PubMed
    1. Stupp R, Dietrich PY, Ostermann Kraljevic S, et al. Promising survival for patients with newly diagnosed glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2002;20(5):1375–1382. - PubMed
    1. Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. The New England journal of medicine. 2005;352(10):987–996. - PubMed
    1. Greaves M, Maley CC. Clonal evolution in cancer. Nature. 2012;481(7381):306–313. - PMC - PubMed

Publication types

MeSH terms

Substances