Phase III Trial Of Radical Chemo-radiation Vs Radiation Alone In The Management Of Localised Bladder TCC.
Funder
National Health and Medical Research Council
Funding Amount
$194,875.00
Summary
This trial aims to see if the combination of Chemotherapy and Radiation treatment is indeed superior in eradicating the tumor and preserving the Bladder in a greater number of patients as compared to Radiation treatment alone. If the final results from this study do show chemoradiotherapy to be significantly superior to radiation alone, without an increase in morbidity ( especially long term side effects ) , this may lay the platform for a greater proportion of patients with localised bladder ca ....This trial aims to see if the combination of Chemotherapy and Radiation treatment is indeed superior in eradicating the tumor and preserving the Bladder in a greater number of patients as compared to Radiation treatment alone. If the final results from this study do show chemoradiotherapy to be significantly superior to radiation alone, without an increase in morbidity ( especially long term side effects ) , this may lay the platform for a greater proportion of patients with localised bladder cancer, being in the first instance considered for this organ( bladder) preserving approach something which has become a reality at a number of other sites of cancer with the use of multimodality treatment.Read moreRead less
Optimising Regulatory T Cell Depletion In Combination With Chemotherapy For Enhanced Anti-tumour Immunity
Funder
National Health and Medical Research Council
Funding Amount
$264,816.00
Summary
The drug cyclophosphamide helps the immune system attack cancer by decreasing the number of immune cells that suppress an immune response to cancer ('Regulatory T cells'). This project combines standard chemotherapy with the drug cyclophosphamide in people with mesothelioma and lung cancer. The aim of the project is to find the dose of cyclophosphamide that maximally decreases Regulatory T cells in each patient, and determine the effect of this on anti-tumour immunity and response to treatment.
Polycomb Group Genes In Murine Lymphomagenesisand Their Impact On Drug Response.
Funder
National Health and Medical Research Council
Funding Amount
$476,815.00
Summary
The success of lymphoma treatment with current drugs is limited by drug resistance. Some crucial links between genes which cause cancer and genes which alter response to cancer treatment have been identified: the cellular machinery that cancer cells use to become cancer cells in the first place, is often the same machinery that cancer cells later use to become resistant to cancer treatments. The Polycomb Group family controls expression of other critical genes: that is, they dictate which genes ....The success of lymphoma treatment with current drugs is limited by drug resistance. Some crucial links between genes which cause cancer and genes which alter response to cancer treatment have been identified: the cellular machinery that cancer cells use to become cancer cells in the first place, is often the same machinery that cancer cells later use to become resistant to cancer treatments. The Polycomb Group family controls expression of other critical genes: that is, they dictate which genes are switched on, where, and when. This determines whether a cell behaves normally or whether it may turn into a cancer cell. When Polycomb Group genes themselves are expressed at the wrong time or place, they can cause cancer. In human lymphoma, these genes have been associated with more aggressive lymphoma. This has also been shown for other cancers such as breast and prostate cancer. In some cases these genes are associated with cancers that do worse following anti-cancer treatment. So far, no research has been published looking the direct impact of the Polycomb Group genes on the success of treatment in a controlled laboratory model. We have used a powerful laboratory mouse model of lymphoma, established in the host laboratory, in which over-expression of the c-myc oncogene in developing B cells causes lymphoma. This model is easy to manipulate and this provides us with a great deal of experimental control, much more than can be achieved from working with patient samples. Two family members, Bmi-1 and Cbx7, cause lymphoma to develop aggressively and we will ask whether two other members, Ezh2 and Rybp do this as well. We will determine whether these 4 genes cause drug resistance in lymphoma, with currently used chemotherapy and also with novel anti-cancer drugs. By increasing our understanding of drug resistance in lymphoma, drugs may be utilised more effectively and new markers identified to predict which drug will be successful in treating a particular lymphoma.Read moreRead less
Pathophysiology Of Oxaliplatin-induced Nerve Dysfunction And Neuropathy
Funder
National Health and Medical Research Council
Funding Amount
$281,255.00
Summary
When treating patients diagnosed with cancer, nerve dysfunction is a common complication of chemotherapy, particularly with oxaliplatin. Neurological symptoms develop in up to 90% of patients following oxaliplatin treatment. Neurotoxicity is a key factor in determining the dosage and frequency of current chemotherapeutic agants. Oxaliplatin therapy results in disabling neurological effects. Onset of neuropathy can be relatively fast or in other cases may develop months after therapy has been com ....When treating patients diagnosed with cancer, nerve dysfunction is a common complication of chemotherapy, particularly with oxaliplatin. Neurological symptoms develop in up to 90% of patients following oxaliplatin treatment. Neurotoxicity is a key factor in determining the dosage and frequency of current chemotherapeutic agants. Oxaliplatin therapy results in disabling neurological effects. Onset of neuropathy can be relatively fast or in other cases may develop months after therapy has been completed. The other chief problems encountered during chemotherapy can be overcome: nausea and vomiting can be treated; myelosuppression can be reversed. End organ toxicity such as neuropathy cannot be controlled. Despite the high incidence of neuropathy due to chemotherapy, the mechanisms involved remain poorly understood, particularly with newer therapies. The aim of the present study is to measure nerve function in oncology patients treated with oxaliplatin using a novel protocol, attempting ultimately to identify aspects of dysfunction that correlate with clinical abnormalities, so helping to pin-point the mechanisms responsible for neuropathy. Once identified, management strategies can be developed to better target the prevention and treatment of neuropathy in oncology patients treated with chemotherapy.Read moreRead less
Role Of Immediate Early Gene Induction And AP-1 Activation In HDAC Inhibitor Induced Apoptosis.
Funder
National Health and Medical Research Council
Funding Amount
$524,820.00
Summary
Histone deacetylase inhibitors (HDACi) are a novel class of anti-tumor agents, recently approved for the treatment of cutaneous T-cell lymphoma. The goal of this study is to improve our understanding of how this class of drug induces tumor cell death. These studies are designed to provide insight into which patients are most likely to benefit from treatment with these agents. Second, they will provide direction into how the therapeutic efficacy of HDACi may be enhanced, through combination with ....Histone deacetylase inhibitors (HDACi) are a novel class of anti-tumor agents, recently approved for the treatment of cutaneous T-cell lymphoma. The goal of this study is to improve our understanding of how this class of drug induces tumor cell death. These studies are designed to provide insight into which patients are most likely to benefit from treatment with these agents. Second, they will provide direction into how the therapeutic efficacy of HDACi may be enhanced, through combination with other existing therapeutics.Read moreRead less
Targeting Adaptive Mechanisms To Endoplasmic Reticulum Stress In Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$511,294.00
Summary
Melanoma is a major Australian health problem, but there is no curative treatment once the disease spreads beyond the skin. We will study the role the response of melanoma cells to stress conditions of an organelle called endoplasmic reticulum in determining sensitivity of melanoma to killing induced by therapeutic drugs. If successful, this study will provide much needed new insights into the resistance of melanoma to treatment and point to new treatment approaches against the disease.
An In-vivo Model Of Acquired Chemoresistance In Small Cell Lung Cancer
Funder
National Health and Medical Research Council
Funding Amount
$363,827.00
Summary
Lung cancer is a common and lethal disease in our community. In this project, we explore how a very aggressive form of lung cancer becomes resistant to chemotherapy. To do this, we use a new mouse model of lung cancer in which we can study how human lung cancer cells develop resistance to chemotherapy in vivo. Understanding these pathways will help us to better treat lung cancer with chemotherapy.
Bcl-2 Proteins And The Regulation Of The Megakaryocyte Lineage.
Funder
National Health and Medical Research Council
Funding Amount
$416,240.00
Summary
Platelets are tiny cells that circulate in the blood. They are essential for blood clotting. Too few platelets leads to uncontrolled bleeding. Platelets are produced in the bone marrow by cells called 'megakaryocytes'. Cancer chemotherapy often causes dangerous decreases in platelet count - this is thought to be because it kills megakaryocytes. We will pinpoint the molecules responsible for megakaryocyte life and death. This has the potential to make the side effects of chemotherapy less severe.
Dissecting Isoform Selectivity Of PI3 Kinase Inhibitors. Uncovering Leads For Rational Drug Design.
Funder
National Health and Medical Research Council
Funding Amount
$518,989.00
Summary
The PI3 kinase enzyme controls many functions in cells and in many cases contributes to the onset and progression of diseases such as cancer, thrombosis and inflammatory diseases. Compounds that block PI3 kinase activity may be useful drugs but will need to act specifically to minimize side effects. We aim to understand the way in which inhibitors block the PI3 kinase activity with the belief that this information will allow us to make better drugs.
Understanding Sensitivity And Resistance To BRAF Inhibitors In Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$484,746.00
Summary
Recent clinical studies have shown that the most common mutation found in melanoma in the gene BRAF can be successfully targeted for treatment. However many patient relapse after early responses and the drug can also cause growth of some skin tumours. This proposal will investigate the reasons for these observations using molecular-imaging and study of tumour tissues and cell lines. This will lead to new insights and better treatments for melanoma and other cancers with BRAF gene mutations.