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.
Treatment for skin cancer costs the Australian healthcare system >$1 billion annually. Early detection and accurate diagnosis of melanoma improves survival, however a standardised approach to diagnosis does not currently exist. This study will prospectively recruit 15,000 patients to develop and validate a risk stratified image-based approach to melanoma prevention, early detection and surveillance which will incorporate cutting edge technologies to standardise diagnosis and optimise care.
Regulation Of Stat1 Activity Levels: Abnormalities In Human Melanoma Cells Resistant To Interferon.
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
Melanoma and its treatment continues to be an important health concern in Australia. The interferons comprise an elaborate system of natural substances produced in the body, one of whose functions is to prevent cancer cells from developing. The interferons have been widely used to treat human diseases including viral infections and cancers like malignant melanoma. However, results of recent trials have cast doubt on its effectiveness. We have found that advanced stage melanoma cells resist the d ....Melanoma and its treatment continues to be an important health concern in Australia. The interferons comprise an elaborate system of natural substances produced in the body, one of whose functions is to prevent cancer cells from developing. The interferons have been widely used to treat human diseases including viral infections and cancers like malignant melanoma. However, results of recent trials have cast doubt on its effectiveness. We have found that advanced stage melanoma cells resist the direct anti-cancer effects of interferons because they have abnormalities in their ability to respond to interferon. We have made good progress in understanding why the melanoma cells do not respond to the interferons. In particular they show a deficiency in the activity of protein, Stat1, required to send the interferon signal inside the cells. The current proposal will allow us to gain a greater understanding of the processes inside cancer cells regulating Stat1 activity and the reasons for its abnormality in interferon resistant cancer cells. This study will help establish an assay to predict which cancer patients will respond to interferon therapy, saving pateints from unecessary discomfort and costs. It will also have a broad significance to many human diseases where abnormalities in interferon signaling occur and will help to bring about ways to produce the necessary changes in cell properties to overcome the abnormalites, restore the responses and improve the application of interferons to treat melanoma and perhaps other human diseases as well.Read moreRead less
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 Lineage Specific Pathway For Progression Of Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$485,746.00
Summary
Melanoma is an insidious cancer, and its incidence has increased dramatically over the past four decades. Melanoma has an almost universally poor prognosis once metastasis has occurred. There are currently no treatment regimens that have a significant impact on prolonging survival or decreasing mortality from metastatic melanoma. Our preliminary data has shown the importance of a factor found in normal melanocytes in control over expression of a separate factor required for invasion and metastas ....Melanoma is an insidious cancer, and its incidence has increased dramatically over the past four decades. Melanoma has an almost universally poor prognosis once metastasis has occurred. There are currently no treatment regimens that have a significant impact on prolonging survival or decreasing mortality from metastatic melanoma. Our preliminary data has shown the importance of a factor found in normal melanocytes in control over expression of a separate factor required for invasion and metastasis of melanoma. These markers could serve as an important diagnostic marker for melanoma. Further, they may be suitable drug targets for the prevention and treatment of metastatic melanoma, and will advance our understanding of how melanoma spreads.Read moreRead less
Effects Of Nevogenesis Susceptibility Genes And Phenotypic Correlation With Dermoscopic Characteristics Of Nevi
Funder
National Health and Medical Research Council
Funding Amount
$554,099.00
Summary
Melanoma is a form of skin cancer that arises from the cells that produce pigment and is a major public health issue in Australia. We will examine the relationship between the form, structure and colour of existing types of moles and their subsequent risk of developing into melanoma. This will be the first study to combine dermoscopy, a non-invasive examination technique, with DNA tests of the genes that determine skin, hair and eye colour, aiding in the early prediction and diagnosis of skin ca ....Melanoma is a form of skin cancer that arises from the cells that produce pigment and is a major public health issue in Australia. We will examine the relationship between the form, structure and colour of existing types of moles and their subsequent risk of developing into melanoma. This will be the first study to combine dermoscopy, a non-invasive examination technique, with DNA tests of the genes that determine skin, hair and eye colour, aiding in the early prediction and diagnosis of skin cancer.Read moreRead less
Immunological Mechanisms Of Clinical Responsiveness To Immunotherapy For Metastatic Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$480,750.00
Summary
There have been no major improvements in the treatment of most metastasizing, solid tumours in the last several decades. One avenue that has received much attention is boosting a cancer patient's immune system with an anti-cancer vaccine, so that it destroys just the cancerous cells. This has proved an elusive goal, and no treatment has ever been shown to be of repeated worth, in the complete resolution of multiple sites of metastatic disease, until now. Two consecutive trials of our dendritic c ....There have been no major improvements in the treatment of most metastasizing, solid tumours in the last several decades. One avenue that has received much attention is boosting a cancer patient's immune system with an anti-cancer vaccine, so that it destroys just the cancerous cells. This has proved an elusive goal, and no treatment has ever been shown to be of repeated worth, in the complete resolution of multiple sites of metastatic disease, until now. Two consecutive trials of our dendritic cell based vaccine, which uses only cells from the patient to be treated, have each shown a 15% complete, durable, response rate. The remissions have now lasted longer than 3 years in patients otherwise expected to survive less than 1 year, with no serious side effects observed in any of the patients treated. It is likely that part of the success of this treatment is that it targets unique mutations in the patient's own cancer cells, in combination with a powerful immune stimulation from the dendritic cells. In contrast, most carefully run trials, now and in the recent past, have attempted to use more generic targets, common to many patients' cancers. The problem with this approach is likely to be that the patient is tolerant to these, since the targets are common, self proteins. At variance with all previous trials, we found an exact correlation between durable clinical responses and the degree of anti-tumour immunity displayed by the patients T cells. This grant proposal is based on the reasoning that, by studying in depth the characteristics of this successful immune response, in patients with complete, durable, clinical responses, we will be able to make major improvements in the formulation of the therapy.Read moreRead less
Comprehensive Assessment Of Genetic And Environmental Risk Factors For Melanoma: A Population-based Family Study
Funder
National Health and Medical Research Council
Funding Amount
$150,679.00
Summary
Excessive sunlight can cause melanoma, a serious type of skin cancer. However, there are other factors including a person's genetic make-up that are thought to put some people at higher risk. Many 'healthy' people have small changes in their genes that might make them more likely to develop melanoma. We need to know more about these genetic factors. Our study will investigate how particular small genetic changes influence a person's likelihood of developing melanoma.