The Paediatric Cancer Research Program is a collaborative initiative bringing together researchers and clinicians across Hudson Institute of Medical Research, Monash Children’s Hospital, Monash Children’s Cancer Centre and Monash University. The Paediatric Cancer Research Program aims to improve outcomes in children diagnosed with cancer through innovative research into the development and progression of these diseases and identification of new and more effective therapeutic strategies. Research interests currently include: Atypical Teratoid Rhabdoid Tumour (AT/RT); Diffuse Intrinsic Pontine Glioma (DIPG); Ependymoma; Leukaemia; Malignant Rhabdoid Tumour (MRT); Medulloblastoma; Neuroblastoma; Osteosarcoma; Wilm’s tumour
A team of researchers from Hudson Institute, Monash University and Monash Children’s Cancer Centre is advancing our knowledge of a rare and deadly paediatric brain cancer, Diffuse Intrinsic Pontine Glioma (DIPG). DIPG is a highly aggressive cancer that occurs in the brainstem, most frequently in children between the ages of five and nine. There is currently no effective treatment and most children die within a year of diagnosis. Research into DIPG has been severely hindered by the rarity of the disease, absence of suitable human tumour material, and a lack of reliable preclinical models. This project aims to further define the molecular mechanisms underlying the development and progression of this devastating disease. The team will develop a series of novel in vitro and in vivo preclinical models using new and established human cell lines, human fetal astrocytes and neural stem cells, and genetically modified mice.
Malignant Rhabdoid Tumor (MRT) and Atypical Teratoid Rhabdoid Tumors (ATRT) are rare aggressive cancers which primarily affect the kidney and central nervous system of young children. These cancers are characterised by the inactivation of the gene, SMARCB1.
Dr Jason Cain, co-Head of the Developmental and Cancer Biology lab at Hudson Institute’s Centre for Cancer Research, in collaboration with PhD student Dean Popovski and Deakin University, has been investigating the potential of a novel epigenetic therapy, histone deactylsae inhibitors (HDACi), to treat MRT. “We knew from previous studies that the SMARCB1 protein has a role in histone acetylation, which provided the rationale for this research” said Dr Cain.
Published in the American Association for Cancer Research journal Clinical Cancer Research in January 2016, Dr Cain’s research used human MRT cell lines and xenografted mouse models and found that low-doses of HDACi treatment can stop the growth of MRT cells, reduce their ability to self-renew and drive tumour cell differentiation.
“Other studies have used toxic doses of HDACi, but we tested the drug both in vitro and in vivo and discovered that low doses are just as effective. It’s early days, but we think this new approach for treating MRT warrants further investigation” said Dr Cain.