The Roles Of EZH2 And FOXO1A In CNS-PNET Pathogenesis.
Funder
National Health and Medical Research Council
Funding Amount
$467,517.00
Summary
Although CNS-PNETs are the most common embryonal CNS tumours of childhood and cause significant mortality and morbidity, there is a very limited understanding of the pathogenesis of this aggressive disease. This situation is a major handicap to the development of more specific and effective therapies. While a better understanding of the fundamental pathology of CNS-PNETs will have immediate diagnostic implications, the elucidation of the biochemical pathways that are disrupted in these tumours w ....Although CNS-PNETs are the most common embryonal CNS tumours of childhood and cause significant mortality and morbidity, there is a very limited understanding of the pathogenesis of this aggressive disease. This situation is a major handicap to the development of more specific and effective therapies. While a better understanding of the fundamental pathology of CNS-PNETs will have immediate diagnostic implications, the elucidation of the biochemical pathways that are disrupted in these tumours will facilitate the design of new drugs that are specifically directed towards the critical proteins in these pathways. The identification of specific genes and-or pathways that are deregulated in CNS-PNET cells is essential for the development of safer, more directed, and more effective therapies that are urgently required for the treatment of those with this devastating disease.Read moreRead less
Primary central nervous system (CNS) tumours, arising in the brain and spinal cord, are the leading cause of cancer-related deaths in children less than 15 years of age. Medulloblastomas and other primitive neuroectodermal tumours (PNETs) are the most common form of primary childhood brain tumours, accounting for 25-30% of cases. Despite notable recent advances in our understanding of the molecular genetic basis of malignancies, the pathogenesis of CNS PNETs remains obscure. To address this prob ....Primary central nervous system (CNS) tumours, arising in the brain and spinal cord, are the leading cause of cancer-related deaths in children less than 15 years of age. Medulloblastomas and other primitive neuroectodermal tumours (PNETs) are the most common form of primary childhood brain tumours, accounting for 25-30% of cases. Despite notable recent advances in our understanding of the molecular genetic basis of malignancies, the pathogenesis of CNS PNETs remains obscure. To address this problem, we propose to apply a novel combinatorial approach for the identification of PNET tumour suppressor genes utilising both representational difference analysis (RDA) and microarray expression profiling. Data from this study will help to elucidate the molecular pathways that are compromised in the initiation and growth of PNETs. This information will have direct implications for the development of improved diagnostic and prognostic indicators necessary for the design of more effective therapeutic strategies for the treatment of PNET patients.Read moreRead less
Development Of A Scorpion Toxin For Tumour Imaging
Funder
National Health and Medical Research Council
Funding Amount
$529,577.00
Summary
The aim of this project is to develop a tool for visualising tumours during surgery. Surgical removal of tumours remains the foundation of cancer treatment, but the ability to distinguish the margin between cancerous and healthy cells is imprecise. We will explore the potential of a scorpion toxin that selectively targets cancer cells, as a tumour imaging agent. This project has the potential to dramatically enhance patient survival as a result of improving treatments for cancer.
The Intersection Between Hedgehog And Notch Signalling In Medulloblastoma.
Funder
National Health and Medical Research Council
Funding Amount
$620,647.00
Summary
Brain tumours are the second most common malignancy of childhood and the leading cause of cancer related death and disability in children. Medulloblastoma is the most frequent malignant childhood brain tumour, arising in the cerebellum. This application looks at the relationship between two genetic pathways responsible for medulloblastoma which are also drug targets. Understanding this interaction will lead to better treatment options for the disease.
Identification Of Genes Causing Medulloblastoma By Transposon Mutagenesis.
Funder
National Health and Medical Research Council
Funding Amount
$621,997.00
Summary
Brain tumours are the most common cause of cancer-related death in children and the tumour medulloblastoma is the most frequent. There is a need to develop new therapeutic approaches to treating medulloblastoma through the development of new drugs to directly target the tumour. This research has identified new genes that are good candidates as drug targets for treating medulloblastoma.
Testing Novel Therapies Using Paediatric Brain Tumour Models
Funder
National Health and Medical Research Council
Funding Amount
$384,023.00
Summary
Brain tumours are the second most common childhood cancer, with 300 children affected in Australia each year. Many children with brain tumours continue to die of their disease, whilst survivors are often left with devastating life long side effects. Our goals are to harness the power of innovative model systems of childhood brain tumours, in order to test the effectiveness of new treatments for these devastating diseases, so that the most promising therapies can be taken through to the clinic.
The Role Of Patched/Hedgehog Signalling In Common Human Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$495,750.00
Summary
Mutations in the patched -hedgehog pathway are responsible for most of the common skin cancer basal cell carcinoma and some of the brain tumour medulloblastoma. Despite this knowledge we still do not know which cell in the skin gives rise to the basal cell carcinoma, and which cell in the brain gives rise to medulloblastoma. This application describes an approach using animal models to answer these questions and therefore further our understanding of how a normal cell becomes a tumour cell. In a ....Mutations in the patched -hedgehog pathway are responsible for most of the common skin cancer basal cell carcinoma and some of the brain tumour medulloblastoma. Despite this knowledge we still do not know which cell in the skin gives rise to the basal cell carcinoma, and which cell in the brain gives rise to medulloblastoma. This application describes an approach using animal models to answer these questions and therefore further our understanding of how a normal cell becomes a tumour cell. In addition this proposal extends out current studies to examine new gene family members in large tumour collections.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
The Downstream Targets Of Patched/Hedgehog Signalling.
Funder
National Health and Medical Research Council
Funding Amount
$423,055.00
Summary
The patched-hedgehog gene pathway is disturbed in common human cancer, including basal cell carcinoma of the skin, medulloblastoma, rhabdomyosarcoma and ovarian fibroma. This application proposes to look at the genes turned off and on by the patched gene. By identifying these genes and examining their function we will identify the exact genetic disturbance which results in a large proportion of common human cancer. Once we find these genes this opens up the possibilities of designing drugs which ....The patched-hedgehog gene pathway is disturbed in common human cancer, including basal cell carcinoma of the skin, medulloblastoma, rhabdomyosarcoma and ovarian fibroma. This application proposes to look at the genes turned off and on by the patched gene. By identifying these genes and examining their function we will identify the exact genetic disturbance which results in a large proportion of common human cancer. Once we find these genes this opens up the possibilities of designing drugs which specifically block the action of the geneticdefect and thereby treating the tumours.Read moreRead less