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
. 2017 Apr;14(2):372-384.
doi: 10.1007/s13311-017-0524-0.

Brain Cancer Stem Cells in Adults and Children: Cell Biology and Therapeutic Implications

Tamara J Abou-Antoun  1 , James S Hale  2 , Justin D Lathia  2   3   4 , Stephen M Dombrowski  5
Affiliations
Review

Brain Cancer Stem Cells in Adults and Children: Cell Biology and Therapeutic Implications

Tamara J Abou-Antoun et al. Neurotherapeutics. 2017 Apr.

Abstract

Brain tumors represent some of the most malignant cancers in both children and adults. Current treatment options target the majority of tumor cells but do not adequately target self-renewing cancer stem cells (CSCs). CSCs have been reported to resist the most aggressive radiation and chemotherapies, and give rise to recurrent, treatment-resistant secondary malignancies. With advancing technologies, we now have a better understanding of the genetic, epigenetic and molecular signatures and microenvironmental influences which are useful in distinguishing between distinctly different tumor subtypes. As a result, efforts are now underway to identify and target CSCs within various tumor subtypes based on this foundation. This review discusses progress in CSC biology as it relates to targeted therapies which may be uniquely different between pediatric and adult brain tumors. Studies to date suggest that pediatric brain tumors may benefit more from genetic and epigenetic targeted therapies, while combination treatments aimed specifically at multiple molecular pathways may be more effective in treating adult brain tumors which seem to have a greater propensity towards microenvironmental interactions. Ultimately, CSC targeting approaches in combination with current clinical therapies have the potential to be more effective owing to their ability to compromise CSCs maintenance and the mechanisms which underlie their highly aggressive and deadly nature.

Keywords: Cancer stem cells; Childhood brain tumors; Epigenetics; Glioblastoma; Microenvironment; Therapeutic implications.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Cancer stem cells
Fig. 2
Fig. 2
Plasticity and therapeutic implications. CSC = cancer stem cell
Fig. 3
Fig. 3
Autocrine and paracrine loops
Fig. 4
Fig. 4
Age-related tumor frequency. PDGFRA = platelet-derived growth factor receptor A; ALT = alanine transaminase; EGFR = endothelial growth factor receptor; IDH1 = isocitrate dehydrogenase 1; TERT = telomerase reverse transcriptase; NF1 = Neurofibromatosis type 1
Fig. 5
Fig. 5
Resistance to cytotoxic DNA damaging agents
See this image and copyright information in PMC

References

    1. Ostrom QT, Gittleman H, de Blank PM, et al. American Brain Tumor Association. Adolescent and young adult primary brain and central nervous system tumors diagnosed in the United States in 2008–2012. Neuro Oncol. 2016;Suppl 1:i1–i50. - PMC - PubMed
    1. Vigneswaran K, Neill S, Hadjipanayis CG. Beyond the World Health Organization grading of infiltrating gliomas: advances in the molecular genetics of glioma classification. Ann Transl Med. 2015;3:95. - PMC - PubMed
    1. Jelsma R, Bucy PC. The treatment of glioblastoma multiforme of the brain. J Neurosurg. 1967;27(5):388–400. - PubMed
    1. Weller M, Cloughesy T, Perry JR, Wick W. Standards of care for treatment of recurrent glioblastoma—are we there yet? Neuro Oncol. 2013;15:4–27. - PMC - PubMed
    1. Lathia JD, Mack SC, Mulkearns-Hubert EE, Valentim CLL, Rich JN. Cancer stem cells in glioblastoma. Genes Develop. 2015;29:1203–1217. - PMC - PubMed