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Review
. 2017 Jun;17(2):255-263.
doi: 10.1007/s40268-017-0180-1.

Revisiting CDK Inhibitors for Treatment of Glioblastoma Multiforme

Affiliations
Review

Revisiting CDK Inhibitors for Treatment of Glioblastoma Multiforme

Dorota Lubanska et al. Drugs R D. 2017 Jun.

Abstract

Despite extensive efforts and continual progress in research and medicine, outcomes for patients with high-grade glioma remain exceptionally poor. Over the past decade, research has revealed a great deal about the complex biology behind glioma development, and has brought to light some of the major barriers preventing successful treatment. Glioblastoma multiforme (GBM) (stage 4 astrocytoma) is a highly dynamic tumour and one of the most extreme examples of intratumoural heterogeneity, making targeting with specific therapeutics an inefficient and highly unpredictable goal. The cancer stem cell hypothesis offers a new view on the possible mechanisms dictating the heterogeneous nature of this disease and contributes to our understanding of glioma resistance and recurrence. Revealing cell division characteristics of initiating cell populations within GBM may represent novel treatment targets and/or the effective repurposing of existing therapies. In this review, we discuss the potential role of targeting the cyclin-dependent kinases (CDKs) driving this specific population. We also describe developments using multi-omic approaches that may aid in stratifying patient populations for CDK inhibitor therapy.

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Conflict of interest statement

Funding

This work is supported by the Canadian Cancer Society Research Institute Innovation to Impact Grant # 703877.

Conflict of interest

The authors have no conflicts to declare.

References

    1. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352:987–996. doi: 10.1056/NEJMoa043330. - DOI - PubMed
    1. Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009;10:459–466. doi: 10.1016/S1470-2045(09)70025-7. - DOI - PubMed
    1. Beug H. Breast cancer stem cells: eradication by differentiation therapy? Cell. 2009;138:623–625. doi: 10.1016/j.cell.2009.08.007. - DOI - PubMed
    1. Klonisch T, Wiechec E, Hombach-Klonisch S, Ande SR, Wesselborg S, Schulze-Osthoff K, Los M. Cancer stem cell markers in common cancers—therapeutic implications. Trends Mol Med. 2008;14:450–460. doi: 10.1016/j.molmed.2008.08.003. - DOI - PubMed
    1. Kim SH, Ezhilarasan R, Phillips E, Gallego-Perez D, Sparks A, Taylor D, Ladner K, Furuta T, Sabit H, Chhipa R, et al. Serine/threonine kinase MLK4 determines mesenchymal identity in glioma stem cells in an NF-kappaB-dependent manner. Cancer Cell. 2016;29:201–213. doi: 10.1016/j.ccell.2016.01.005. - DOI - PMC - PubMed

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