5005385_DeanPopovskiPhDThesis25475819.pdf (168.65 MB)

Investigation into the Biology of Human Malignant Rhabdoid Tumour

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thesis
posted on 16.05.2017, 23:54 by DEAN POPOVSKI
My study focused on Malignant Rhabdoid Tumor (MRT) a resistant pediatric cancer where the primary mutation is loss of SMARCB1, implicating epigenetic deregulation as central to the pathogenesis of the disease. We demonstrated that repurposing the HDACi inhibitor Panobinostat (LBH589) was able to drive multi-lineage differentiation in MRT cells in vitro and in vivo. Further mechanistic analysis revealed that SMARCB1-restoration mirrored low-dose HDACi treatment in vitro and in vivo. Finally, we discerned that potential mechanistic driver of impair lineage maturation in MRT was EZH2, with targeted therapies of catalytic and non-catalytic function demonstrating improved responses in preclinical models of MRT.

History

Principal supervisor

Jason Edward Cain

Year of Award

2017

Department, School or Centre

Molecular and Translational Sciences

Campus location

Australia

Course

Doctor of Philosophy

Degree Type

Doctorate

Faculty

Faculty of Medicine Nursing and Health Sciences

Exports

Keyword(s)

Exports