Selective Therapies Targeting Tumour Vasculature Of Colorectal Liver Metastases
Funder
National Health and Medical Research Council
Funding Amount
$519,279.00
Summary
Cancer of the bowel is the second highest cause of cancer related deaths in Australia. Over 70% of these deaths are due to bowel cancer spread to the liver or liver metastases. Treatment options for the majority of patients with liver spread are limited. Although chemotherapies are a standard treatment option, they cause significant side-effects as they are small in size and thereby distributed to both cancer and normal tissue. Given the limitations of chemotherapy, our objective is to investiga ....Cancer of the bowel is the second highest cause of cancer related deaths in Australia. Over 70% of these deaths are due to bowel cancer spread to the liver or liver metastases. Treatment options for the majority of patients with liver spread are limited. Although chemotherapies are a standard treatment option, they cause significant side-effects as they are small in size and thereby distributed to both cancer and normal tissue. Given the limitations of chemotherapy, our objective is to investigate two new strategies which selectively destruct tumours with minimal effect to normal tissues. Cancer growth is dependent on an efficient blood supply. One strategy uses drug delivery systems (DDS) to selectively target cancers by exploiting the unique properties of tumour blood vessels. The second strategy uses vascular targeting agents (VTA's) which act on tumour vessels to reduce blood flow and starve the tumour of oxygen, leading to its destruction. We will be testing two agents: SMA-Pirarubicin, a DDS and an innovative VTA, Oxi4503, in an animal model of colorectal cancer liver metastases. Although these drugs are successful in destroying the majority of tumour cells, they have a patchy effect and do not completely destroy the cancerous growth. The varied effects of these agents may be due to variations in tissue hypoxia, tumour vessel structure or factors which trigger blood vessel formation and breakdown. These features will be investigated using techniques established within our laboratory. We will also investigate the combined effect of other novel agents and hyperbaric oxygen administration to improve the effectiveness of these drugs. A successful outcome will result in the development of an improved treatment method which targets tumours, producing maximum destruction with minimum side-effects. This has the potential to replace standard chemotherapies as the preferred treatment for patients with bowel cancer spread, with overall significant patient benefits.Read moreRead less
Polo Kinase Function And The Treatment Of Drug Resistant Tumours.
Funder
National Health and Medical Research Council
Funding Amount
$559,894.00
Summary
Death from cancer often results from tumours becoming resistant to chemotherapy drugs. Some cancers, particularly the common bowel cancers, have high levels of drug resistance that seem to be caused by loss of the controls that act during normal cell division. We will assess whether a recently developed therapeutic approach will kill these drug resistant cancer cells and identify factors that can be targeted to increase the potency and specificity of the therapy.
MMP13 is upregulated in cancer cells and in the tissue that forms around the cancer (stroma). A new MMP13-specific inhibitor reduces breast cancer growth in a mouse model, both at the primary site and also in bone. We will determine the role of MMP13 made by the cancer cells and stroma, respectively, extend the inhibitor work, and identify proteins being cleaved by MMP13. Being a late-stage manifestation, bone metastasis may represent an important clinical trial setting for MMP inhibitors.
VCAM-targeted Delivery Of Recombinant CD39 To The Endothelium Is Antithrombotic, Antiinflammatory And Ameliorates Ischaemia Reperfusion Injury.
Funder
National Health and Medical Research Council
Funding Amount
$623,327.00
Summary
Blockage of arteries with clots leads to heart attacks and strokes. Reestablishment of blood supply by clot-busting drugs or mechanical interventions paradoxically causes further organ injury. This is due to toxic chemicals generated by inflammatory processes and free oxygen radicals. We have created an unique drug that selectively targets blood vessels that are injured by process. The drug will deliver blood-thinning activity and reduce inflammatory stress selectively at the site of need.
This research draws together my expertise in medicinal chemistry, biochemistry, pharmacology and virology to design and develop new compounds that we can use to interrogate and regulate human and viral proteins that cause disease. Protein, cell and animal studies relevant to major 21st century health burdens (such as inflammatory, infectious and metabolic diseases, cancer, pain and viral infections) will provide important new information on mechanisms of disease development and drug action.
The Retina As A Chemogenetic Target For The Treatment Of Depression
Funder
National Health and Medical Research Council
Funding Amount
$408,768.00
Summary
Treatments for depression are often poor because they lack selectivity. By inserting receptors that respond to an inert drug, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) can turn on-or-off very specific classes of cells, providing an exciting treatment direction for depression and other neuropsychiatric diseases. The long term goal of this project is to create a highly effective DREADD-based treatment for depression, which is activated by either eye drops or a pill.
Development Of Systemic Therapies To Improve Response And Prevent Resistance In The Treatment Of Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$569,219.00
Summary
This program of research utilises the unique resources at Melanoma Institute Australia (MIA) to understand the biology of prolonged response and resistance to novel drug therapies used in metastatic melanoma, a cancer that now leads the field in the discovery of new targets for therapeutic manipulation. This program also aims to create new methods to efficiently test and develop drug therapy combinations in humans to improve patient outcomes further or prevent metastatic melanoma altogether.
Risk Stratification And Early Interventions In Pulmonary Vascular Disease: From Acute Pulmonary Embolisms To Chronic Pulmonary Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$99,682.00
Summary
Pulmonary embolism (PE) is a common, potentially life-threatening condition with up to 50% of survivors developing long-term complications, which are associated with breathlessness, functional limitation and risk of premature death if not diagnosed and treated promptly. This project investigates the use of non-invasive scan techniques and exercise testing for early detection of these complications. The project will also explore new drug targets to treat these complications.
Personalised Treatment In Melanoma: Matching Optimal Drug Therapies For Individual Patients To Improve Survival.
Funder
National Health and Medical Research Council
Funding Amount
$132,743.00
Summary
The best treatment for melanoma currently is immunotherapy. However, most patients become resistant to immunotherapy after an initial response. When this occurs, patients are treated with new medications, often in a clinical trial. Unfortunately, doctors cannot predict if a patient is going to respond to a particular new treatment. This project will study the makeup of individual melanomas and use this to recommend which new treatment is most likely to work for the patient.
A Phase I Study Of The First In Class Dual IMiD/bromodomain Inhibitor N-methyl-2-pyrrolidone (NMP) In Relapsed And Refractory Multiple Myeloma.
Funder
National Health and Medical Research Council
Funding Amount
$551,061.00
Summary
We have newly discovered that a simple molecule called NMP has the ability to control myeloma cells that have become resistant to other available treatments. NMP works by enhancing immune function and by killing myeloma cells directly by inhibiting survival signals. NMP is different from all other types of available myeloma treatments. We intend to test the safety and power of NMP in the treatment of myeloma by running a clinical trial of NMP in patients with relapsed myeloma.