University of Cambridge > > Seminars on Quantitative Biology @ CRUK Cambridge Institute  > Targeting the brain tumour stem cell phenotype with small molecules

Targeting the brain tumour stem cell phenotype with small molecules

Add to your list(s) Download to your calendar using vCal

If you have a question about this talk, please contact Florian Markowetz.

Brain cancer patients with glioblastoma multiforme have a very poor prognosis with an average life expectancy of only 12 to 17 months. These tumours are heterogeneous and extremely difficult to treat due to tumour cell invasion of healthy brain tissue and resistance of the malignant cells to conventional therapy. The cellular aggressiveness within brain tumours has been attributed to a subpopulation of tumour cells that possess stem cells-like features. Unlike differentiated tumour cells, so called glioma stem cells (GSCs) possess the ability to give rise to new tumour mass from few if not single cells after surgical debulking of the tumour. The molecular mechanisms underlying this malignant growth are poorly understood and we have used functional genomics to identify critical factors (i.e. TRRAP ) that maintain GSCs in an undifferentiated and tumourigenic state. The evolving notion of cancer cell heterogeneity has important implications for GSC -directed therapy. We investigate the plasticity of the ‘stemness’ phenotype in the context of small molecule-induced differentiation and apoptosis. For example, we analyzed GSC fate upon treatment with the small molecule KHS101 using a panel of molecularly distinct GSC lines that were derived from clinically diverse patient tumours. The small molecule KHS101 induces autophagic cell death in GSCs and eradicates the GSC phenotype in a dose-dependent fashion by down-regulating the expression of GSC maintenance factors (i.e. NOS2 ). Overall, our data suggest that KHS101 is a potential therapeutic option for the treatment of primary and recurrent GBM .

This talk is part of the Seminars on Quantitative Biology @ CRUK Cambridge Institute series.

Tell a friend about this talk:

This talk is included in these lists:

Note that ex-directory lists are not shown.


© 2006-2023, University of Cambridge. Contact Us | Help and Documentation | Privacy and Publicity