Journal
CELLS
Volume 10, Issue 5, Pages -Publisher
MDPI
DOI: 10.3390/cells10051182
Keywords
glioma stem cells; cyclin-dependent kinases; CDK inhibitors; recurrent GBM; CYC065; THZ1; CD133; CD44
Categories
Funding
- European Union [766069]
- Irish Association for Cancer Research (IACR Educational Grant)
- Science Foundation Ireland (SFI) [16/RC/3948, 16/RI/3740]
- European Regional Development Fund
- FutureNeuro
- Science Foundation Ireland (SFI) [16/RI/3740] Funding Source: Science Foundation Ireland (SFI)
- Marie Curie Actions (MSCA) [766069] Funding Source: Marie Curie Actions (MSCA)
Ask authors/readers for more resources
This study highlights the potential of using transcriptional CDK inhibitors to prevent tumor recurrence, particularly in aggressive adult brain tumor GBM. The expression of GSC markers CD133 and CD44 is significantly upregulated in GBM patient tumors, and GSCs are more sensitive to transcriptional CDK inhibitors.
Glioma stem cells (GSCs) are tumour initiating cells which contribute to treatment resistance, temozolomide (TMZ) chemotherapy and radiotherapy, in glioblastoma (GBM), the most aggressive adult brain tumour. A major contributor to the uncontrolled tumour cell proliferation in GBM is the hyper activation of cyclin-dependent kinases (CDKs). Due to resistance to standard of care, GBMs relapse in almost all patients. Targeting GSCs using transcriptional CDK inhibitors, CYC065 and THZ1 is a potential novel treatment to prevent relapse of the tumour. TCGA-GBM data analysis has shown that the GSC markers, CD133 and CD44 were significantly upregulated in GBM patient tumours compared to non-tumour tissue. CD133 and CD44 stem cell markers were also expressed in gliomaspheres derived from recurrent GBM tumours. Light Sheet Florescence Microscopy (LSFM) further revealed heterogeneous expression of these GSC markers in gliomaspheres. Gliomaspheres from recurrent tumours were highly sensitive to transcriptional CDK inhibitors, CYC065 and THZ1 and underwent apoptosis while being resistant to TMZ. Apoptotic cell death in GSC subpopulations and non-stem tumour cells resulted in sphere disruption. Collectively, our study highlights the potential of these novel CKIs to induce cell death in GSCs from recurrent tumours, warranting further clinical investigation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available