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.
The critical role of the class III histone deacetylase SIRT2 in stabilizing N-Myc oncoprotein. Cancer is the commonest cause of death from disease in children. Neuroblastoma is the commonest solid tumor in early childhood. This project will investigate the critical roles of SIRT2 protein in increasing the expression of N-Myc oncoprotein and consequently inducing neuroblastoma, and SIRT2 inhibitors as anticancer agents.
Mitochondrially targeted anti-cancer drugs modulate the mitochondrial genome. Successful cancer management requires novel therapeutical approaches. This project will test the effect of a new class of compounds that target mitochondria, the powerhouse of the cells, where they suppress expression of mitochondrial genes. By this mechanism, cancers that are resistant to apoptosis induction can be inhibited.
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.
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.
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.
Molecular hallmarks of androgen receptor targeting in prostate cancer. There is a critical need in oncology drug development for better biomarkers of response to prostate cancer therapies, clinically to assist with treatment decision making, and pre-clinically to facilitate translation of emerging agents into clinical practice. Using a unique explant culture model, this project will identify protein and lipid markers that can be used to accurately and reliably assess response to androgen recepto ....Molecular hallmarks of androgen receptor targeting in prostate cancer. There is a critical need in oncology drug development for better biomarkers of response to prostate cancer therapies, clinically to assist with treatment decision making, and pre-clinically to facilitate translation of emerging agents into clinical practice. Using a unique explant culture model, this project will identify protein and lipid markers that can be used to accurately and reliably assess response to androgen receptor (AR)-targeting therapies in human prostate tumours. The identification and functional assessment of these biomarkers will identify those that can be used as surrogate endpoints in clinical trials, facilitate earlier approval of investigational agents and lead to improved options for therapeutic management of prostate cancer.Read moreRead less
Targeting A Master Regulator Of Tumour Cell Plasticity As A New Adjuvant Therapy For Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$780,338.00
Summary
Prostate cancer (PCa) claims the lives of over 3,000 Australian men each year. This highlights the urgent need to identify new molecular targets that can be developed as additional therapies for men with PCa. Our team has identified the protein, Zeb1, to be highly expressed in aggressive and treatment resistant forms of PCa. This study aims to characterise the role of Zeb1 in the lethal progression of PCa and to develop a new therapeutic agent to inhibit the production of ZEB1 by cancer cells.