Revisiting CDK Inhibitors for Treatment of Glioblastoma Multiforme.
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.
Department of Biological Sciences, University of Windsor, 401 Sunset Ave, Biology rm. 201, Windsor, ON, N9B 3P4, Canada.
Dorota
D
Lubanska
Department of Biological Sciences, University of Windsor, 401 Sunset Ave, Biology rm. 201, Windsor, ON, N9B 3P4, Canada. lporter@uwindsor.ca.
Lisa
L
Porter
D000818:Animals; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*
D047428:Protein Kinase Inhibitors; D018844:Cyclin-Dependent Kinases