Therapeutic Targeting Of MYCN Oncoprotein Stability In Neuroblastoma
Funder
National Health and Medical Research Council
Funding Amount
$590,206.00
Summary
A high level of MYCN protein is a major indicator of aggressive neuroblastoma (NB) but unfortunately there have been many barriers to the design of targeted therapies. We have identified a protein called PA2G4 which is a cofactor for MYCN in promoting cancer cell growth. We have developed a compound which inhibits PA2G4 and MYCN protein levels and reduces tumour growth. We will examine how PA2G4 cause aggressive tumour characteristics and test new methods to block PA2G4.
More Effective Therapeutic Targeting Of High Risk Childhood Cancer: Neuroblastoma As A Model
Funder
National Health and Medical Research Council
Funding Amount
$6,601,220.00
Summary
Cancer is the commonest cause of death from disease in Australian children. Childhood neuroblastoma is a particularly aggressive cancer, for which new treatment approaches are urgently needed. The team aims to discover better safer therapies for children with this cancer, conducting clinical trials using new drugs and novel drug combinations. We will also investigate novel ways of targeting neuroblastoma cells and identify therapeutic targets in neuroblastoma-initiating cells.
A Novel Molecular Target Capable Of Abrogating Neuroblastoma Development
Funder
National Health and Medical Research Council
Funding Amount
$802,499.00
Summary
Although modern chemotherapy has significantly improved survival rates for many childhood cancers, the outlook remains dismal for children with advanced staged neuroblastoma. These patients frequently have alterations in the cancer-causing gene called MYCN. Using pre-clinical models of MYCN-driven neuroblastoma and genome sequencing we have discovered a gene that can completely block the action of MYCN and prevent neuroblastoma growth. This work will characterize the function of this novel gene.
Optimising Targeted Polyamine Depletion For Treatment Of Childhood Neuroblastoma And Brain Tumours
Funder
National Health and Medical Research Council
Funding Amount
$928,152.00
Summary
Paediatric neuroblastoma and brain tumours, which often have dismal outcomes despite intensive therapy, have high levels of polyamines, which are essential for cell growth. We have shown that depleting polyamines, combined with chemotherapy, represents a highly promising therapy for neuroblastoma. We will make this exciting new treatment approach even more effective by comparing three ways of enhancing polyamine depletion, as a precursor to future neuroblastoma and brain tumour clinical trials.
Functional Characterization And Therapeutic Targeting Of The Novel Long Noncoding RNA RP1-40E16.9
Funder
National Health and Medical Research Council
Funding Amount
$673,447.00
Summary
Cancer is the most common cause of death from diseases in children. Neuroblastoma is the most common solid tumour in early childhood. In this project, we will define the role of a novel long non-protein-coding RNA in promoting neuroblastoma initiation and progression. We will also define the anti-cancer efficacy of a novel therapy targeting the long non-protein-coding RNA.
Targeted Inhibition Of Multidrug Resistance-associated Protein 4 (MRP4) As A Therapeutic Strategy For Childhood Neuroblastoma
Funder
National Health and Medical Research Council
Funding Amount
$602,503.00
Summary
We have shown that a high tumour level of the gene, MRP4, confers a particularly poor outcome in children with the aggressive cancer neuroblastoma. Our results suggest that MRP4 can drive the growth of neuroblastoma cells, and that it does so by removing from the cancer cell a compound that normally regulates key cellular responses including survival and differentiation. We will explore this, and will also test promising inhibitors of MRP4 with therapeutic potential, that we have developed.
Targeting JMJD6 Gene Gain For The Therapy Of Neuroblastoma
Funder
National Health and Medical Research Council
Funding Amount
$381,012.00
Summary
Cancer is the most common cause of death from disease in children. Neuroblastoma is the most prevalent solid tumour in early childhood. In this project, we will define the key role of JMJD6 gene gain in neuroblastoma cell proliferation, survival and tumourigenesis. We will also identify a novel therapeutic strategy for the treatment of neuroblastoma.
Targeted Inhibition Of Polyamine Synthesis For Treatment Of Childhood Neuroblastoma
Funder
National Health and Medical Research Council
Funding Amount
$576,605.00
Summary
The childhood cancer, neuroblastoma, frequently has a dismal outcome despite the use of intensive therapy. Polyamines are molecules that are essential for cell survival and these are increased in aggressive neuroblastoma. Using pre-clinical models, we have shown that inhibiting polyamine production can significantly delay neuroblastoma growth. This project aims to improve the overall efficacy of this treatment by targeting multiple steps in polyamine synthesis in combination with chemotherapy.
Improved Outcomes For Children With Cancer Through Improved Target Identification And Drug Discovery: Neuroblastoma As A Model
Funder
National Health and Medical Research Council
Funding Amount
$6,394,247.00
Summary
The majority of children with neuroblastoma still die of their disease, and survivors have serious side-effects of cancer treatment. We aim to discover better therapies for children with this cancer, conducting clinical trials using existing and new drugs in novel combinations. We will also investigate novel ways of targeting neuroblastoma cells, and study possible prevention strategies for this and other embryonal cancers. This work will have application in other childhood and adult cancers.