Glioma stem cell signaling: therapeutic opportunities and challenges

Abstract

The field of cancer research has experienced significant momentum from the discovery that most malignant tumors harbor subpopulations of cancer cells with stem cell features. Consequently, identification and characterization of so-called ‘cancer-initiating cells’ or ‘cancer stem cells’ has also provided novel insights into the biology of malignant brain tumors. Despite an ongoing debate regarding the exact role and identity of cancer stem cells, several studies have suggested that this subpopulation is critical for tumor initiation, tumor progression, angiogenesis and resistance to available therapies. The study of signaling pathways critical to normal neural stem and progenitor cells has also increased our understanding of the mechanisms that drive cancer stem cell-associated tumorigenesis and tumor progression. Novel treatment strategies are being developed to selectively target the molecular pathways relevant to cancer stem cells. This review summarizes important signaling pathways employed by both normal and cancer stem cells and highlights promising molecular-targeted therapies interfering with those signaling pathways in malignant gliomas.

Keywords::

• angiogenesis
• β-catenin
• Bmi1
• brain tumors
• cancer stem cells
• EGF
• glioblastoma
• miRNA
• neural stem cells
• notch
• PDGF
• receptor tyrosine kinases
• signaling
• Sonic hedgehog
• VEGF
• Wnt

Acknowledgements

The authors gratefully acknowledge the support of the Joanna Bruner Brain Tumor Research Foundation.

Financial and competing interests disclosure

Jörg Dietrich is a recipient of the Paul Calabresi Career Development Award for Clinical Oncology (NIH K-12). This work has been supported by the Stephen E and Catherine Pappas Foundation Award for Brain Tumor Research (to Jörg Dietrich), by an NIH K-08 award (CA124804, to Santosh Kesari), a Sontag Foundation Distinguished Scientist Grant (to Santosh Kesari), and the James S McDonnell Foundation (to Santosh Kesari). Santosh Kesari has been a member of the speaker’s bureau for Enzon and has received research funding from Adnexus, Bristol-Myers Squibb and Novartis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.