Genetic And Environmental Factors In Invasive Cervical Cancer: A Twin Study.
Funder
National Health and Medical Research Council
Funding Amount
$769,637.00
Summary
Cervical cancer (neck of womb) is caused by human papillomavirus (HPV). Most women clear this very common virus. However persistent HPV infection can cause abnormal changes to cervical cells as found on Pap smears. Genetic factors may determine why such women ultimately develop cancer. A way to evaluate environmental from genetic effects is to study twins. If the risk is greater in indentical twins as compared to nonidentical it is more like to be due to genetics.
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.
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.
Development Of Novel EGFR Tyrosine Kinase Inhibitors For The Management Of Glioma, Head And Neck And Other Cancers
Funder
National Health and Medical Research Council
Funding Amount
$196,527.00
Summary
Abnormalities in EGF-EGFR family signalling pathways have been implicated in many human cancers including glioma, squamous cell carcinome of the head and neck, colon, ovary and prostate, and are associated with poor clinical prognosis, non-responsiveness to chemotherapy, and decreased survival. Inhibitors of these pathways would therefore be useful anti-cancer pharmaceuticals. This proposal outlines experiments aimed at understanding the role of the individual EGFR family members in controlling ....Abnormalities in EGF-EGFR family signalling pathways have been implicated in many human cancers including glioma, squamous cell carcinome of the head and neck, colon, ovary and prostate, and are associated with poor clinical prognosis, non-responsiveness to chemotherapy, and decreased survival. Inhibitors of these pathways would therefore be useful anti-cancer pharmaceuticals. This proposal outlines experiments aimed at understanding the role of the individual EGFR family members in controlling a complex signalling network, and the development of novel small molecule inhibitors of these pathways which are specific for individual EGFR family members and which should prove effective in the management of many forms of cancer. Additionally, the potential synergy of these inhibitors in combination therapy with other anti-cancer drugs and reagents which induce cell death will be investigated. These small molecule pharmaceuticals could easily be produced commercially, and taken into clinical trials, in Australia.Read moreRead less
Treatment Of Virally-induced Cancers By RNA Interference.
Funder
National Health and Medical Research Council
Funding Amount
$389,250.00
Summary
Cancers require certain mutations and the over expression of genes to cause disease. Each cancer has a unique set of gene changes thus making it difficult to treat. However, it has become clear that the normal control mechanisms of many cancers are still intact but are repressed by the over expression of these oncogenes (or cancer genes). By turning off these oncogenes we can restore normal control to the cell and the cancer will die normally. We will use a new method of gene targeting called RN ....Cancers require certain mutations and the over expression of genes to cause disease. Each cancer has a unique set of gene changes thus making it difficult to treat. However, it has become clear that the normal control mechanisms of many cancers are still intact but are repressed by the over expression of these oncogenes (or cancer genes). By turning off these oncogenes we can restore normal control to the cell and the cancer will die normally. We will use a new method of gene targeting called RNA interference to turn off oncogenes. RNA interference involves treatment of cells with a small peice of genetic material that provides the cell with an identity pattern of the gene to be eliminated. The cell takes the pattern and turms off the genes expression. As long as the pattern only turns off the cancer gene all other genes will remain normal. We will test this using cervical cancer as a model as all these cancers are caused by infection with a virus that carries 2 oncogenes. It is these virus oncogenes that cause the cancer and therefore we know the exact target genes that need to be turned off. Most importantly these genes are not present in normal cells making it safe to target them by RNA interference. We have gathered an expert group of investigators with experience in cervical cancer and cancer genetics to address this problem. If successful we will have proven this new technique can work against cervical cancer and this method could then be applied to any cancer. We would then be able to start human trials. Cervical cancer kills over 300 women in Australia each year, is the leading cause of cancer death in Aboriginal women, is 2nd most common cancer of women in the world and is the leading cancer killer worldwide in women under 50.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
Conditional Knockout Of The Murine Patched Gene For The Study Of Skin Differentiation And Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$423,564.00
Summary
Basal cell carcinoma (BCC) is the most common cancer in Australia. We recently isolated the BCC gene, Patched (PTCH) from analysis of patients with Naevoid Basal Cell Carcinoma Syndrome (NBCCS). Individuals with NBCCS have a wide variety of developmental defects in addition to a cancer predisposition which includes medulloblastoma, rhabdomyosarcoma and ovarian fibroma as well as multiple BCCs. This application proposes the generation of an animal model for skin development and cancer by selectiv ....Basal cell carcinoma (BCC) is the most common cancer in Australia. We recently isolated the BCC gene, Patched (PTCH) from analysis of patients with Naevoid Basal Cell Carcinoma Syndrome (NBCCS). Individuals with NBCCS have a wide variety of developmental defects in addition to a cancer predisposition which includes medulloblastoma, rhabdomyosarcoma and ovarian fibroma as well as multiple BCCs. This application proposes the generation of an animal model for skin development and cancer by selectively removing patched gene function from specific cell of the skin. In doing this we will be able to determine the exact role of this gene in skin development, and how mutation causes common skin cancer.Read moreRead less