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.
Towards Better Treatments For Acral Melanoma Through Functional Genomics
Funder
National Health and Medical Research Council
Funding Amount
$1,456,823.00
Summary
Acral melanoma is an uncommon melanoma subtype with bad prognosis that has been poorly characterised at the molecular level. The project will conduct comprehensive analysis of acral melanoma at the DNA, RNA and protein levels. Through subsequent functional follow-up studies of key drivers of this cancer type we will identify novel drug targets to treat this disease.
Development Of Follistatin As Novel Cancer Therapeutic
Funder
National Health and Medical Research Council
Funding Amount
$494,324.00
Summary
In this project, we aim to rapidly commercialise our discovery that Follistatin, an endogenous hormone, can dramatically improve the efficacy of platinum-based chemotherapy in lung cancer.
The FGFR Family As Drivers And Biomarkers Of Regorafenib Response In Gastric Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$670,784.00
Summary
The drug regorafenib has recently emerged as a potential new treatment for patients with gastric (stomach) cancer. We have discovered that gastric cancer cell lines which express high levels of members of the FGFR family are highly sensitive to this drug. This project will define the potential of targeting the FGFR family in gastric cancer,the value of FGFR1-4 as markers of regorafenib response, and develop strategies for enhancing regorafenib activity in this difficult to treat disease.
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.
Osteosarcoma is the most common tumour of bone. Recent success in targeting immune checkpoint blockers such as Programmed death-1 (PD-1) in genomically complex tumours suggests that osteosarcomas may be amenable to such strategies. We will characterise the role of the PD-1 pathway in osteosarcoma development and growth. Using preclinical mouse models we will investigate the biology of the PD-1 pathway and study its potential as a therapeutic target in advanced and resectable osteosarcoma.
BRCA-P: An International Randomised Phase III Study Evaluating The RANK Ligand Inhibitor Denosumab For The Prevention Of Breast Cancer In BRCA1 Mutation Carriers
Funder
National Health and Medical Research Council
Funding Amount
$2,589,049.00
Summary
Women with a faulty BRCA1 gene are at high lifetime risk for breast cancer. Identifying a safe and effective prevention therapy is therefore a ‘holy grail’. We have discovered that denosumab, used to treat osteoporosis or breast cancer spread to bone, could be ‘repurposed’ as a prevention drug. BRCA-P is an international randomised controlled study that will determine if denosumab prevents breast cancer. Associated translational research will facilitate swift transfer to the clinic.
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.
Identification Of PACE-1 As A Novel Therapeutic Target For The Treatment Of Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$606,144.00
Summary
Advanced prostate cancer (PCa) remains the major therapeutic challenge since neither surgery nor systemic therapies are effective at this stage. Recently, we identified a protein called PACE-1 that is essential for PCa cell survival. We plan to investigate the roles of PACE-1 in the development and progression of prostate cancer. We will then test if PACE-1 inactivation alone or in combination with systemic cancer therapies will inhibit prostate tumor growth and disease progression.