The Molecular Basis For The Initiation Of Squamous Differentiation And How It Is Disrupted In Oral Cancers
Funder
National Health and Medical Research Council
Funding Amount
$64,631.00
Summary
Squamous cancers of the mouth, nose and throat occur due to defects in the cells that line these regions. We have shown that a major defect is that the lining cells are unable to stop growing and mature into cells that provide a barrier against the environment. In this proposal we will undertake studies to identify why these cancers cells do not mature properly. In doing so we will be able to identify new strategies that may be used to treat patients with this frequently deadly cancer.
E2F Inhibitors As Anticancer Agents For Squamous Cell Carcinoma
Funder
National Health and Medical Research Council
Funding Amount
$257,036.00
Summary
Squamous cell carcinoma of the head and neck is one of the six most frequent causes of cancer death worldwide. these tumours are currently treated with surgery, radiotherapy and chemotherapy. Although these treatments are associated with a five year survival rate of between 40% and 60% there is a critical need for more effective and less destructive treatments. In this application we will extend on our earlier work in which we identified the protein E2F1 as being a major contributor to tumour de ....Squamous cell carcinoma of the head and neck is one of the six most frequent causes of cancer death worldwide. these tumours are currently treated with surgery, radiotherapy and chemotherapy. Although these treatments are associated with a five year survival rate of between 40% and 60% there is a critical need for more effective and less destructive treatments. In this application we will extend on our earlier work in which we identified the protein E2F1 as being a major contributor to tumour development. In normal cells, E2F1 is required for the regulated growth of head and neck cells. However, we found that in head and neck tumours, E2F1 is overactive and contributes to the dergulated growth of the tumour. In this project we will test our newly developed inhibitors of E2F1 on various tumour cells derived from head and neck cancers to see how effective they are at stopping tumour cell growth. Furthermore we will test these compounds in animal models of head and neck cancer to determine whether they will be useful therapeutic agents for treatment of human cancer. Early results on tumour cell lines look very promising.Read moreRead less
Development Of A Novel Therapy For The Treatment Of Epidermal Squamous Cell Carcinoma
Funder
National Health and Medical Research Council
Funding Amount
$432,750.00
Summary
Squamous cell carcinomas (SCC) are the most common life-threatening form of skin cancer in Australia. SCCs commonly arise in areas of the body that have been exposed to excessive amounts of UV irradiation. The cells of the skin from which SCCs are derived are called keratinocytes. UV irradiation causes lesions within these cells such that their growth and maturation are disrupted leading to deregulated growth and maturation and hence tumour formation. We have previously identified a protein, E2F ....Squamous cell carcinomas (SCC) are the most common life-threatening form of skin cancer in Australia. SCCs commonly arise in areas of the body that have been exposed to excessive amounts of UV irradiation. The cells of the skin from which SCCs are derived are called keratinocytes. UV irradiation causes lesions within these cells such that their growth and maturation are disrupted leading to deregulated growth and maturation and hence tumour formation. We have previously identified a protein, E2F, that is central to this process and whose inhibition leads to decreased cancer cell growth. During the course of these studies we noted that the deregulation of E2F could also lead to the disruption of keratinocyte maturation. This led us to propose that the inhibition of E2F in SCCs may result in both decreased cancer cell growth as well as the reinstatement of a normal maturation process. this would make E2F inhibitors a very attractive therapeutic for treating SCC. In the present study we aim to explore the ability and the mechanism by which E2F modulates keratinocyte proliferation and maturation. This will be done in vitro as well as in animal models of SCC. These studies will be required in order to take the E2F inhibitors into clinical trials.Read moreRead less
A Novel Tumour Suppressor Function Of E2F7 In Squamous Cell Carcinoma Formation
Funder
National Health and Medical Research Council
Funding Amount
$524,124.00
Summary
squamous cell carcinomas of the skin are the second most common skin cancer. In this proposal we present data showing that a new gene, E2F7, may play an important role in the development of squamous cell carcinoma. If true, these studies will identify a new therapeutic target that could be exploited in developing novel anticancer therapies.
Role Of Brm In Skin Tumour Progression From Benign To Malignant
Funder
National Health and Medical Research Council
Funding Amount
$457,267.00
Summary
Australia has the highest incidence of skin cancer in the world. Skin cancer is 3 times as common as all other cancers combined and continues to increase in incidence, particularly in the aging population. Skin cancer is caused by exposure to the ultraviolet radiation found in sunlight. Ultraviolet radiation causes the appearance of solar keratosis, or sunspots, benign lesions that are not particularly dangerous to human health. Some of these develop into malignant squamous cell carcinomas that ....Australia has the highest incidence of skin cancer in the world. Skin cancer is 3 times as common as all other cancers combined and continues to increase in incidence, particularly in the aging population. Skin cancer is caused by exposure to the ultraviolet radiation found in sunlight. Ultraviolet radiation causes the appearance of solar keratosis, or sunspots, benign lesions that are not particularly dangerous to human health. Some of these develop into malignant squamous cell carcinomas that can spread to other tissues and are potentially fatal. Little is known about the biological mechanisms involved in solar keratosis development into squamous cell carcinomas. We have identified the gene brm as being involved in this process. It has not previously been recognised that this gene is important for skin cancer development and therefore our preliminary studies have identified a potential new target. We will study the role of this gene in ultraviolet radiation induced skin carcinogenesis, determine whether it is mutated by ultraviolet radiation in human skin cancer, and what role in plays in some key biological processes in skin cancer development. This study will expand our understanding of malignant conversion during human skin carcinogenesis, the most prevalent human cancer in Australia.Read moreRead less
Preclinical Development Of Q2361, A Transforming New Drug For Skin Cancer Prevention In Organ Transplant Recipients
Funder
National Health and Medical Research Council
Funding Amount
$724,957.00
Summary
Patients that receive organ transplants need additional medications in order to prevent organ rejection. Unfortunately, these drugs carry an unwanted side-effect - they permit the development of skin cancer. Currently, other than surgery, little can be done to help these patients. Our preliminary data suggest that a new drug may prevent these skin cancers from forming. This project aims to deliver key insights into the influence of this drug and its role in skin cancer prevention.
Oral Cancer is a devastating disease that is associated with poor survival and greatly impacts the lives who do survive. This project aims to develop a tool to inspect the changes of molecules called microRNAs, in saliva and skin cells of the mouth, collected using a simple, painless method, which will help to predict the risk of patients developing oral cancer.
Post-operative Concurrent Chemo-radiotherapy Versus Post-operative Radiotherapy In High Risk Cutaneous Squamous Cell Carcinoma Of The Head And Neck
Funder
National Health and Medical Research Council
Funding Amount
$252,000.00
Summary
Squamous cell carcinoma of the skin is one of the most common cancers affecting Australians. The majority are readily cured with simple local therapy, such as surgery. However some patients develop advanced disease requiring surgery and post-operative radiotherapy. Despite this, some patients do not achieve cure. This study aims to improve cure rates for these patients by comparing post-operative radiotherapy (control arm) to post-operative chemo-radiotherapy(experimental arm).
Skin cancer affects 60% of Australians. Nicotinamide (vitamin B3) prevents many of sunlight’s damaging effects and reduces premalignant keratoses by 35% compared to placebo in sun-damaged individuals. We now need to test whether nicotinamide can prevent skin cancer. Skin cancer patients will receive nicotinamide or placebo for 12 months and new cancers will be counted in each group. Nicotinamide is safe, widely available and an exciting opportunity for cost-effective skin cancer prevention.
Identification Of Critical Factors For The Establishment And Maintenance Of The Epidermal Barrier
Funder
National Health and Medical Research Council
Funding Amount
$671,424.00
Summary
The human skin plays a crucial role in the body’s defence against our hostile environment. The outer most layer of the skin, the epidermis is essential for formation and repair of the skin barrier. We have identified a family of genes that are pivotal for skin development and function. Disruption of these genes has disastrous consequences, including loss of barrier function and the development of skin cancers. This project examines how these diseases occur.