A Preclinical Model Of Relapse In Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$573,515.00
Summary
Leukaemia is the most common type of cancer in children but resistance to therapy continues to be a significant problem. This project will investigate the biology of drug-resistance and relapse using a mouse model that replicates the human disease. We hope to identify novel therapeutic targets that can be used in combination with existing therapies to improve outcomes in this disease. We also hope to identify markers that can be used to screen for patients at increased risk of relapse.
Dual Targeting Of The Androgen Receptor For Effective And Durable Control Of Lethal Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$946,177.00
Summary
Preventing binding of androgens to the androgen receptor is the mainstay treatment for advanced prostate cancer, but resistance inevitably develops and the disease becomes lethal. We will develop a new drug that targets a part of the androgen receptor unrelated to its androgen binding function to overcome resistance to current therapy. As this drug will be effective in all stages of prostate cancer, it has high potential to improve survival outcomes for men with prostate cancer.
Real-time Optical Window Imaging Of AKT-FRET Biosensor Mice To Maximise PI3K/AKT Drug Targeting Within The Hypoxic Microenvironment Of Pancreatic Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$683,447.00
Summary
Inefficient drug response in solid tumour tissue is often a limiting factor in the clinical effectiveness of cancer therapies. Using cutting-edge imaging technology and 3D models that mimic the disease, we have mapped areas of poor drug response within distinct regions of tumours with low oxygen levels known as hypoxia. Here, we will specifically target factors limiting efficient drug targeting in these areas to improve the encouraging anti-cancer profile of AKT inhibitors in pancreatic cancer.
PARP And PI3K Inhibition In Pancreatic Cancer: Intravital Insights And ‘fine-tune’ Priming Using AKT And Single/double-strand DNA Break Biosensor Mice.
Funder
National Health and Medical Research Council
Funding Amount
$760,505.00
Summary
Inefficient drug response in solid tumour tissue is often a limiting factor in the clinical effectiveness of cancer therapies. Using cutting-edge imaging technology and 3D models that mimic the disease, we can map areas of poor drug response within distinct regions of tumours with chemotherapy. Here, we will shift factors limiting efficient drug targeting in these areas to improve the encouraging anti-cancer profile of PI3K and DNA repair inhibitors in pancreatic cancer.
Identifying And Exploiting Novel Pharmacological Targets For Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$431,000.00
Summary
Breast cancers are made up of different types of cancer cells, and not all cells contribute equally. A subset of cancer cells may be uniquely capable of driving tumor growth, rebuilding fatal tumors after therapy and establishing new tumors at distant sites. Identifying and exploiting the pathways that regulate the activity and survival of these cells will lead to better modes of treatment, and move towards a relapse-free future for breast cancer patients.
I am a cancer cell biologist investigating molecular mechanisms of leukaemia cell resistance to chemotherapeutic drugs, and novel strategies for the management of high risk or relapsed disease. For these purposes I have developed orthotopic xenograft mode
Activation Of BMP4 Signalling To Inhibit Breast Cancer Metastasis
Funder
National Health and Medical Research Council
Funding Amount
$748,742.00
Summary
The spread of cancer cells to other organs is a common cause of breast cancer-related death in women. Current therapies for advanced breast cancer are often palliative since the secondary tumours become resistant to the chemotherapy. Here, we are using preclinical models of advanced breast cancer to develop a treatment that should be effective in patients with secondary tumours and should reduce the risk of dying of this disease.
ADAM Metalloprotease Inhibition For Treatment Of Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$770,925.00
Summary
Colorectal cancer (CRC) causes over 4000 deaths/year, typically from developing drug resistance and spreading to other organs (metastasis). These processes involve tumour cells called cancer stem cells (CSCs), which rely on specific cell surface proteins for survival and function. We are developing antibodies against one of these type of proteins, to test in mouse models of CRC. These already show promise in targeting CSCs and inhibiting drug-resistance and metastasis in mice.
Targeting Microtubules To Overcome Chemoresistance In Pancreatic Cancer
Funder
National Health and Medical Research Council
Funding Amount
$594,336.00
Summary
Pancreatic cancer is a devastating disease with a dismal prognosis because it is extremely resistant to chemotherapy agents. We plan to examine the expression of proteins called microtubules in pancreatic cancer and assess their role in drug resistance. It is anticipated that the findings of these studies will lead to the development of effective approaches to sensitise the cancer cells to chemotherapy agents.
Multidrug Resistance Protein 1 Inhibitors To Sensitise Cancers To Chemotherapy
Funder
National Health and Medical Research Council
Funding Amount
$840,166.00
Summary
Multidrug resistance protein 1 (MRP1) is often present at high levels in cancer cells, where it pumps chemotherapy drugs back out, causing drug resistance. Inhibitors that block MRP1 would increase the effectiveness of chemotherapy. We have developed MRP1 inhibitors with promising activity in cancer cells and mouse tumours and will now develop these inhibitors for clinical application and commercialisation.