Guest Speakers - 

Sourav Banerjee, PhD, University of Dundee

Discussion - 

"An atypical, secreted kinase promotes the ‘seed and soil’ of high-grade brain cancer "

In 2015, the highly atypical secretory pathway kinase Fam20C was shown to phosphorylate the majority of extracellular proteins at S-x-E/pS sites. We found that Fam20C expression is specifically increased in high-grade glioma (GBM), with higher Fam20C expression correlating with significantly poorer patient survival. Intriguingly, GBM cells lacking Fam20C showed a dramatic reduction in proliferation and failed to form tumours efficiently following implantation into the brains of immunocompromised mice. These findings suggested that Fam20C directly promotes the tumour-forming capacity of GBM cells—the ‘seed’.

Furthermore, mice with a brain-specific Fam20C knockout survived significantly longer following GBM implantation than mice with normal brain Fam20C expression, providing evidence that Fam20C also contributes to the tumour microenvironment—the ‘soil’—that supports GBM growth. Consistent with these findings, treatment with a small-molecule transcriptional repressor of Fam20C doubled survival in mice bearing patient-derived xenograft and allograft brain tumours.

Together, these findings establish Fam20C as a potential therapeutic target in GBM and provide a strong rationale for drug discovery. Fam20C is highly atypical and was not inhibited by any canonical kinase inhibitors tested. However, we have identified promising ‘hit’ compounds through an academic screening programme with Novartis. These preliminary findings position us to develop a dedicated Fam20C drug discovery programme, in collaboration with the Drug Discovery Unit at the University of Dundee, to identify and optimise novel Fam20C inhibitors for GBM.

Ira Sharma¹, Febe Ferro¹, Joaquina Nogales¹, Amy Dunne Miller¹, Vasudha Tandon¹, Paul Brennan², Sandra Wiley³, Carolyn Worby³, Sourav Banerjee¹. 

¹Faculty of Health, University of Dundee, Dundee, UK 

²Edinburgh Cancer Centre, University of Edinburgh, Edinburgh, UK 

³Department of Pharmacology, University of California San Diego, La Jolla, USA 

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