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.
Delineating Mechanisms Of Acquired Resistance To Kinase Inhibitors And Devising Novel Strategies To Combat Therapeutic Resistance
Funder
National Health and Medical Research Council
Funding Amount
$437,034.00
Summary
Kinase inhibitors are some of the most successful anti-cancer agents that have emerged in the last 15 years. However, tumors become resistant to these drugs after showing initial response. Understanding mechanisms through which cancer cells become resistant to these drugs will allow us to develop effective strategies to counter it and achieve sustained responses to cancer therapy. I propose to build a research program to systematically study these mechanisms to improve cancer therapeutics.
Toll-like Receptor 2 Signalling As A Potential Therapeutic Target In Gastric Cancer
Funder
National Health and Medical Research Council
Funding Amount
$323,091.00
Summary
Stomach cancer is the fourth most deadly cancer in the world. Stomach cancer is closely linked with inflammation, and we have shown that a key inflammatory molecule, called toll-like receptor 2 (TLR2), can drive the development of stomach cancer. However, this occurs in a non-inflammatory manner. My research aims to understand how TLR2 is involved in the progression of stomach cancer, with the ultimate goal to find an early biomarker of disease, and to develop better therapies.
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.
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.
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
Tailoring Targeted Therapy To DNA Repair-defective High-Grade Serous Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$802,247.00
Summary
Ovarian cancer is a major cause of cancer death in women because current treatments are inadequate. Half of aggressive ovarian cancers have abnormalities in DNA repair and should be susceptible to new PARP inhibitor therapy, yet not all those respond. By developing a new model of studying human ovarian cancers in mice, we can discover markers to predict which ovarian cancers will respond best to these exciting new treatments.
EphA3 Is A Marker Of Glioma Stem/progenitor Cells And A Potential Target For Therapy.
Funder
National Health and Medical Research Council
Funding Amount
$585,860.00
Summary
EphA3 is a cell surface marker which is enriched on glioma ‘propagating’ stem cells (GSCs) and furthermore has a functional role in regulating GSC differentiation and fate determination. EphA3 therefore provides a novel therapeutic target for high-grade glioma.
Overcoming Resistance Of Human Metastatic Melanoma To Treatment
Funder
National Health and Medical Research Council
Funding Amount
$727,758.00
Summary
Melanoma is a major Australian health problem, but there is no curative treatment once the disease spreads beyond the skin. I have been working on “overcoming resistance of melanoma to treatment” continuously for 10 years. My past research has provided a number of insights into the resistance of melanoma to treatment. I wish to extend my work to find new treatment approaches against the disease. If successful, this work will greatly benefit melanoma patients and Australian people.