The effect of Pt binding to CTR1 on Cu homeostasis and cell phenotype. The copper transport protein CTR1 is commonly believed to transport active cisplatin (a platinum-based anticancer agent) into the cell, but this model is inconsistent with the chemical properties of platinum (Pt) and CTR1. The project aims to interrogate the interaction between CTR1 and Pt in cells by developing new chemical tools for the study of Pt species within cells. It will then study the effect of the CTR1-Pt interacti ....The effect of Pt binding to CTR1 on Cu homeostasis and cell phenotype. The copper transport protein CTR1 is commonly believed to transport active cisplatin (a platinum-based anticancer agent) into the cell, but this model is inconsistent with the chemical properties of platinum (Pt) and CTR1. The project aims to interrogate the interaction between CTR1 and Pt in cells by developing new chemical tools for the study of Pt species within cells. It will then study the effect of the CTR1-Pt interaction on copper homeostasis and cell phenotype. It is expected that the results will provide valuable information on the status of CTR1 and Pt following interaction, and reveal whether less toxic complexes are just as effective in decreasing cell malignancy as cisplatin itself.Read moreRead less
Detection of infrared-biomarkers for the diagnosis and treatment of canine neoplasia. This research hopes to discover infrared-biomarkers for canine cancers using synchrotron infrared and laser light. Many dog cancers are similar to human cancers so cancerous tissues and cells from dogs make excellent models for human cancer research. This project will provide new insights and technological approaches to cancer diagnosis and treatment.
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 a cost-effective therapy for osteoporosis using Australian indigenous emu oil. Emu oil has a potent anti-inflammatory property. This project aims to show in rodents whether its use can overcome the inflammatory condition and osteoporosis caused by aging, menopause and cancer chemotherapy. This research could lead to development of an emu oil-based therapy for major health problems and have immense social and economic implications.
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
Novel platinum(IV) complexes that are targeted to and trapped by tumours and tumour cells. Platinum complexes continue to be a mainstay in the treatment of solid tumours and their combination with molecularly targeted agents selected for the type of tumour and the mutations identified is expected to lead to continued growth in their use. However, their toxicity remains a major impediment to their use and effectiveness and therefore, this project aims to develop less toxic analogues that are as l ....Novel platinum(IV) complexes that are targeted to and trapped by tumours and tumour cells. Platinum complexes continue to be a mainstay in the treatment of solid tumours and their combination with molecularly targeted agents selected for the type of tumour and the mutations identified is expected to lead to continued growth in their use. However, their toxicity remains a major impediment to their use and effectiveness and therefore, this project aims to develop less toxic analogues that are as least as effective as current drugs. This project will combine recent developments in stabilisation and cellular trapping of platinum(IV) pro-drugs with a range of strategies designed to limit activation of these pro-drugs to the tumour environment.Read moreRead less
Targeting the delivery of cytotoxic agents to tumour cells using novel minicells as drug delivery vehicles and engineered, bispecific antibodies. Cancer persists as a major cause of morbidity and mortality globally. A major problem is the non-specific action of drugs used for treatment. The minicell is a drug delivery vehicle, capable of packaging a variety of drugs. The project will develop tumour-specific antibodies that will target minicells to tumours, improving cancer survival rates.
EGFR-directed radioimmunotherapy combined with chemotherapy and DNA repair inhibition: development towards clinical application for aggressive cancers. Pancreatic ductal adenocarcinoma (PDAC) and triple negative breast cancer (TNBC) are aggressive diseases which lack effective therapies in clinical use. A novel and curative therapy was developed against PDAC and TNBC which involves targeted radiotherapy combined with chemotherapy and DNA damage response inhibition. This project will develop a “p ....EGFR-directed radioimmunotherapy combined with chemotherapy and DNA repair inhibition: development towards clinical application for aggressive cancers. Pancreatic ductal adenocarcinoma (PDAC) and triple negative breast cancer (TNBC) are aggressive diseases which lack effective therapies in clinical use. A novel and curative therapy was developed against PDAC and TNBC which involves targeted radiotherapy combined with chemotherapy and DNA damage response inhibition. This project will develop a “preclinical data package” comprising a biological rationale and preclinical evidence of safety and efficacy that together would justify an early phase clinical trial. This package includes the choice of formulations, mechanism of action and safety studies. This development will have an immediate impact for PDAC and TNBC patients and a future impact on other EGFR-positive cancers.Read moreRead less
Biophysical identification of natural human antibody targets. A natural human antibody, PAT-SM6, isolated using technology developed by the partner organisation (Patrys), offers promise as a therapy to reduce mortalities due to cancer, the leading cause of death in Australia. The novelty of the approach pioneered by Patrys is the direct production of human antibodies which avoids undesirable side effects associated with the use of antibodies containing non-human components. This project is to ....Biophysical identification of natural human antibody targets. A natural human antibody, PAT-SM6, isolated using technology developed by the partner organisation (Patrys), offers promise as a therapy to reduce mortalities due to cancer, the leading cause of death in Australia. The novelty of the approach pioneered by Patrys is the direct production of human antibodies which avoids undesirable side effects associated with the use of antibodies containing non-human components. This project is to discover the specificity of PAT-SM6 for proteins and protein complexes and how these interactions lead to tumour cell death. This work will enhance the effectiveness of human antibody therapies and help in the development of this fast growing area within the biotechnology industry in Australia.Read moreRead less