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.
Enhancer RNAs As Cancer Drivers And Predictive Biomarkers Of BET Inhibitor Therapy
Funder
National Health and Medical Research Council
Funding Amount
$124,676.00
Summary
BET inhibitors are a new type of therapy designed to slow down cancer growth by switching off cancer genes. In individuals with colon and prostate cancer, BET inhibitors have shown good initial results, but these are not long-lasting. By measuring blood levels of a specific type of RNA (a close companion of DNA), called CCAT1 and PCAT1, we hope to better understand which patients gain the most benefit from BET inhibitors, and the mechanisms that cause BET inhibitors to stop working.
Dissecting The Roles Of Steroid Hormone Receptors In The Mammary Gland
Funder
National Health and Medical Research Council
Funding Amount
$92,314.00
Summary
Breast cancer remains a major cause of death in women, requiring the development of highly efficient therapeutics. Research into the molecular and cellular mechanisms of the normal mammary gland is crucial. This project will increase our understanding of the normal roles of the estrogen and progesterone receptors. This research may have significant implications for clinical studies that use more targeted therapies.
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.
Cyclin E1 As A Therapeutic Target In Women With High-grade Serous Cancer And Primary Treatment Failure
Funder
National Health and Medical Research Council
Funding Amount
$644,170.00
Summary
Ovarian cancer is the 5th most common cancer in women and the most lethal gynaecologic malignancy. We found tumours with extra copies of the CyclinE1 gene (CCNE1) are less likely to respond to standard treatment, and show reliance on its activity. Therefore, targeting CCNE1 may be a novel treatment strategy for these cancers. We will perform preclinical studies with therapeutic inhibitors towards the CCNE1 pathway and further explore the underlying biology of tumours with CCNE1 amplification.
Chronic myeloid leukaemia was almost always fatal before the development of imatinib a decade ago, the first tyrosine kinase inhibitor (TKI) developed to treat a human cancer. There are now more potent TKIs that are effective in cases of resistance to imatinib. The challenge now is to optimise the achievement of remissions using these drugs and convert CML into a curable condition. This will be the focus of my NHMRC Practitioner Fellowship over the next 5 years.