Inhaling asbestos fibres causes cancer (both mesothelioma and lung cancer). These are related to the amount of asbestos inhaled. This study will look at lung tissue removed from people for other medical reasons to see if those at high risk (e.g. construction workers) have benefited from the laws restricting asbestos use. We hope to predict rates of these cancers in the future from these results, based on the numbers of fibres seen in the lungs.
The Impact Of Therapy On T-cell Recognition Of Mutated Tumour Neo-antigens
Funder
National Health and Medical Research Council
Funding Amount
$1,126,685.00
Summary
Cancer is caused by mutations which should be 'seen' and destroyed by the patients immune cells, similar to how immune cells protect us against viruses. But they don't. This grant will study how current cancer treatments help the immune cells 'see' these mutations. We will undertake these studies in the important cancers lung cancer and mesothelioma.
Novel Surgery-chemotherapy-immunotherapy Approaches For Lung Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$662,819.00
Summary
Many patients undergo cancer surgery every year yet still die of cancer over the next few years because the surgeon couldnt remove all of the cancer cells, many of which were undetectable at the time of surgery. This grant will develop ways of combining chemotherapy drugs with immune therapy to 'mop up' hidden residual cancer cells after operations - the immune system, when stimulated appropriately, should be able to 'seek and destroy' those hidden deposits and thus cure these cancers.
Improving Treatment Outcomes For Malignant Mesothelioma Patients Using Biomarkers.
Funder
National Health and Medical Research Council
Funding Amount
$795,262.00
Summary
The deadly asbestos-induced cancer mesothelioma is continuing to kill tens of thousands of people each year. Most patients are diagnosed with advanced disease. In this study we will use novel biomarkers to help the diagnosis of mesothelioma and potentially improve treatment options for patients.
Characterising The Mutations, Signatures, Potential New Therapeutic Targets And Biomarkers In Malignant Mesothelioma Using Whole Genome Analysis.
Funder
National Health and Medical Research Council
Funding Amount
$1,219,288.00
Summary
Malignant mesothelioma is an aggressive tumour that occurs principally in the pleura as a consequence of inhaling asbestos fibres. Currently there is no cure for malignant mesothelioma. Thus new therapeutic approaches are desperately needed. Such new approaches will require a detailed understanding of the genetic lesions of malignant mesothelioma. Therefore we will perform whole genome sequencing of a large cohort of malignant mesothelioma patients to identify mesothelioma-related alterations.
Aberrant Transcriptional Signalling In The Progression And Metastasis Of Melanoma.
Funder
National Health and Medical Research Council
Funding Amount
$353,033.00
Summary
There are currently no treatments that have any impact on decreasing mortality from metastatic melanoma. We have found 2 new variants in melanoma that may control the tumour growing and invading around the body. This study will examine the protein containing these changes with the aims of finding how they function differently, to identify their roles in the formation of melanoma, as well as to identify new targets for prevention and treatment of metastatic disease.
Compartmental Analysis Of T-cell Responses In Thoracic Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$851,403.00
Summary
To improve immune therapy for cancer we have to be able to determine how cancer patients ‘see’ mutated cancer proteins. Blood is the easiest & most useful source of immune ‘killer’ cells for that task, but the lymph node that drains the tumour and the fluid that bathes a tumour probably contain a much higher number of these killer cells than blood. If so, studying them would help us better track responses to therapy and enable us to choose the best mutated proteins for a vaccine.
Reactivities Of CD8 T Cells To Mutated Neo-antigens In Lung Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$661,979.00
Summary
Tumours express mutated proteins (called ‘neo-antigens’) which can be targets of powerful killer T cells which can destroy cancer cells. To understand why these cells fail to cure most cancers we will study neo-antigens identified by modern DNA sequencing methods to identify these neo-antigens & the responses to them. Then it will be possible to design trials in individual patients, e.g. personalised vaccines to ‘force’ the immune system to attack cells bearing these neo-antigens.
Resetting The Tipping Point: Converting Immune Checkpoint Non-responders Into Responders.
Funder
National Health and Medical Research Council
Funding Amount
$455,135.00
Summary
Although immunotherapy has recently shown a breakthrough in the treatment of lung cancers, with long-term full regression of the cancer in some patients, most patients unfortunately do not respond. In this proposal, we want to characterise the events that occur in a cancer that is cured by immunotherapy, while it regresses. By subsequently reinforcing those processes, we aim to tip the balance towards a response, thereby increasing the cure rate.
The Novel CXCR4/CCR7 Heterodimeric Chemokine Receptor Is A Key Determinant Of Breast Cancer Metastasis.
Funder
National Health and Medical Research Council
Funding Amount
$461,252.00
Summary
Novel cellular receptor has been identified that works as a switch to turn on cellular functions that are responsible for the metastatic dissemination of cancer cell to distant organs. The make-up and regulatory mechanisms of this novel receptor will be studied together with its potential utility as the marker of metastatic breast cancer.