Genome Engineered, Preclinical Models Of Serrated Colorectal Cancer To Fast-track A High Sensitivity, Early Detection Test
Funder
National Health and Medical Research Council
Funding Amount
$593,854.00
Summary
1 in 12 Australians will develop colorectal cancer. Here we use information about changes to the genetic (inherited) material of these cancers to develop new, complex models of this disease. This teaches us about what those changes do, and highlights important targets for future drug therapies. We are also developing a better test to detect hidden pre-cancers that are not well detected by our current population screening strategy, to help reduce deaths from this disease.
Role Of A DNA Helicase, Recql4, In Haematopoiesis, Skeletal Biology And Malignancy
Funder
National Health and Medical Research Council
Funding Amount
$750,701.00
Summary
We are interested in understanding how a gene involved in familial cancer works. Mutations in this gene cause patients to develop a range of cancers in their blood and skeleton. We are seeking to understand how this gene functions so that we can understand how the cancers form in these families and also how sporadic cancer forms.
Mediator Kinase As A Therapeutic Target For Wnt/β-catenin Dependent Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$949,907.00
Summary
Colorectal cancer is the third leading cause of cancer mortality in Australia and globally. The Wnt/?-catenin signalling pathway is a well established driver of colon cancer growth in >90% of cases. Using sophisticated genetic screens, we identified CDK8/19 as a colon cancer oncogene and critical regulator of Wnt/?-catenin activity. In this proposal, we will use innovative cancer models in mice and human cancer tissues to investigate newly developed CDK8/19 inhibitors for colon cancer therapy ....Colorectal cancer is the third leading cause of cancer mortality in Australia and globally. The Wnt/?-catenin signalling pathway is a well established driver of colon cancer growth in >90% of cases. Using sophisticated genetic screens, we identified CDK8/19 as a colon cancer oncogene and critical regulator of Wnt/?-catenin activity. In this proposal, we will use innovative cancer models in mice and human cancer tissues to investigate newly developed CDK8/19 inhibitors for colon cancer therapy.Read moreRead less
Stratification Of Therapies In HNSCC Through Discovery Of Molecular Signatures
Funder
National Health and Medical Research Council
Funding Amount
$852,600.00
Summary
Human head and neck cancer is a devastating disease with poor survival rates. Using a unique mouse model, we have now uncovered novel genetic defects that trigger cancer development. These defects are also evident in human cancers. This proposal will utilize this mouse model to explore new treatment strategies based on targeting the genetic defect. Ultimately we anticipate that this will translate into personalized therapies that will favourably alter the course of this cancer.
Tracking The Origins And Drivers Of Metastasis In Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$1,022,600.00
Summary
Prostate cancer is now the most commonly diagnosed cancer but only 10% of men with it, will die from it. Our current ability to discriminate between cancers with an indolent course and those that are lethal is poor. This project will examine the mixture of tumour clones (subclones) that are present in prostate cancers and define and track those cancer subclones that break away from the prostate and lodge in distant sites, causing death.
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.
Expanding Diagnostic Approaches For Lynch Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$1,269,355.00
Summary
Currently, there are ~1,000 families who have attended Family Cancer Clinics across Australia who have the hallmarks of having Lynch syndrome, a hereditary bowel cancer syndrome, but who have no gene defect identified, i.e. their cancer is unexplained. Clinicians are challenged by these “Lynch-like” patients as their family cancer risk is unknown. Our research has identified new gene defects in Lynch-like patients. Our aim is to optimise clinical testing approaches for Lynch-like patients.
Determining The Origin Of Lethal Metastases In Multifocal Primary Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$696,470.00
Summary
New biomarkers are required to accurately predict lethal prostate cancer from benign, indolent disaese that doesn't require expensive treatment. To do this relies on finding molecular differences between disease states. Advancements in high throughput genomic technologies enables us to now probe the lethal prostate cancer genome and transcriptome and distinguish this disease state from other forms of prostate cancer.
Translation Of PALB2 Genetic Information Into Breast Cancer Clinical Genetic Services
Funder
National Health and Medical Research Council
Funding Amount
$423,081.00
Summary
Today in Australia women attending clinical genetics services and receiving genetic counselling due to a personal and/or family history of breast cancer are not considered for testing of PALB2 despite mounting evidence that the risk of breast cancer in mutation carriers is at least as high as the risk for BRCA2 mutation carriers. This project will provide the evidence base to support the incorporation of PALB2 gene testing into routine clinical genetics services both in Australia and around the ....Today in Australia women attending clinical genetics services and receiving genetic counselling due to a personal and/or family history of breast cancer are not considered for testing of PALB2 despite mounting evidence that the risk of breast cancer in mutation carriers is at least as high as the risk for BRCA2 mutation carriers. This project will provide the evidence base to support the incorporation of PALB2 gene testing into routine clinical genetics services both in Australia and around the world.Read moreRead less
Circulating Tumour DNA Analysis Of Acquired Treatment Resistance In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$511,807.00
Summary
Taxanes are commonly used chemotherapeutic agents in breast cancer, yet treatment resistance remains a significant clinical problem for which new approaches are needed. Many cancers shed small amounts of DNA (circulating tumor DNA (ctDNA)) into the bloodstream, and analysis of ctDNA can allow assessment of tumour specific genomic changes occurring during treatment. This project aims to utilise ctDNA to study acquired treatment resistance to taxane-based chemotherapy in metastatic breast cancer.