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Results: 39

A MOUSE MODEL OF HIST1H3B / ACVR1 MUTANT DIPG

Diffuse intrinsic pontine glioma (DIPG) is a malignant brainstem tumour arising in children representing a major unmet clinical need, with a 2-year survival rate close to zero. With chemotherapy ineffective and surgical intervention not possible, new therapeutic approaches are urgently needed based upon the unique biological mechanisms driving DIPG tumorigenesis. ...

An open label single arm phase I/II study of ...

We propose a phase I/limited efficacy clinical trial investigating repeated administration of MTX110, a soluble form of panobinostat, given via convection-enhanced delivery (CED) to pediatric patients with newly diagnosed diffuse intrinsic pontine glioma (DIPG). We hypothesize this therapy will be safe and well-tolerated and will be efficacious and prolong ...

EPIGENETIC ALTERATIONS AS THERAPEUTIC TARGETS IN PEDIATRIC BRAIN TUMORS

We and others co-discovered the presence of activating mutations in ACVR1 in 25% of human DIPGs in 2014. Subsequently, my laboratory has developed a murine DIPG model incorporating R206H ACVR1 and observed that R206H ACVR1 significantly accelerates brainstem gliomagenesis. In addition, short-term treatment with a bone morphogenetic protein pathway inhibitor (...

Cellular Cybercriminals: DIPG Hacks into the Neural Communication Infrastructure

 My group has recently demonstrated the neuronal activity drives the growth of DIPG and other high-grade gliomas. One way that active neurons promote DIPG growth is through activity-regulated secretion of growth factors into the tumor microenvironment. We have now discovered an additional, surprising means of neuron:glioma communication – ...

Combinatorial Strategies Alongside ACVR1 Inhibition in DIPG

 We and others recently discovered a novel cancer gene, ACVR1, to be mutated in approximately 25% diffuse intrinsic pontine glioma (DIPG), most commonly in the youngest patients, and co-segregating with K27M mutations in histone H3.1 (HIST1H3B/HIST1H3C). ACVR1 encodes a receptor serine/threonine kinase mutated ...