Event:

Glioblastoma (GBM) is a devastating disease and the most lethal of adult brain tumours. Despite standard surgery, radiation and chemotherapy, the median survival is 15 months, thought to be due, in part, to recurrence from a small reservoir of brain tumour initiating cells. Our laboratory discovered adult neural stem cells, now found to be present in the brains of all adult mammals, through the development of the clonal neurosphere assay. This assay has contributed to the identification of adult brain tumour stem cells (BTSCs), which may represent a reservoir that leads to GBM recurrence and death. We have developed a unique cellular resource of more than 120 BTSC lines derived from GBM patients.

Building upon the identification of growth factors and cytokines that converge on the cytoplasmic signal transducer and activator of transcription 3 (STAT3) to maintain the adult neural stem cell undifferentiated state, and the fact that STAT3 is abnormally active in GBM and may be one of the causes of tumour growth and therapeutic resistance, a new research focus has emerged for our laboratory. Collaborative studies with academic and industry partners has resulted in the identification of promising therapeutic candidates that target janus kinase (JAK)/STAT3 signalling in GBM. These compounds both attenuate growth of BTSCs in cell culture and prolong the survival of immunocompromised mice that have received BTSC xenografts. These findings support our overall hypothesis that targeting of the STAT3 signalling pathway may represent an effective therapeutic approach to managing GBM.

Supported by the Alberta Cancer Foundation and the Networks of Centres of Excellence – Stem Cell Network.