Targeting Tumour Angiogenesis In Breast Cancer By Altering MicroRNA Signalling
Funder
National Health and Medical Research Council
Funding Amount
$660,151.00
Summary
Despite advances in treatment, breast cancer remains one of the leading underlying causes of death and disability in Australia. Preventing cancer spread therefore has the potential for enormous economic and social outcomes. Small RNAs have recently been identified as key regulators of cancer cell biology. This project seeks to take a leadership role in the area of small RNA biology by targeting small RNAs implicated in blood vessel formation as a means of suppressing breast cancer spread.
Parathyroid Hormone-related Protein (PTHrP), Common Genetic Variants In The PTHrP Gene (PTHLH), And Breast Cancer Risk And Survival
Funder
National Health and Medical Research Council
Funding Amount
$120,253.00
Summary
In a partnership between Peter MacCallum Cancer Centre, St Vincent's Hospital, and The University of Melbourne, we are investigating the role of PTHrP, a peptide integral to the growth and spread of Cancer. Initially thought to facilitate cancer spread, recent studies suggest it may actually be protective. In a new approach, we will analyse new DNA databases and patient data from around the world. We hope to extend our understanding of PTHrP, and perhaps find novel drug and therapeutic targets.
Targeting FLT3 Kinase Activity To Treat Haematopoietic Neoplasms
Funder
National Health and Medical Research Council
Funding Amount
$673,045.00
Summary
Most leukaemias are incurable so it is important to find new treatments. For this to occur it is essential that the mutated genes that cause leukaemia are identified. We have generated a mouse with a mutation in a gene called c-Cbl that promotes the activation a protein called FLT3 that is involved in the development of many types of leukaemias. By treating mutant mice a drug that specifically suppresses the function of FLT3 we intend to identify the most effective treatments for human leukaemia ....Most leukaemias are incurable so it is important to find new treatments. For this to occur it is essential that the mutated genes that cause leukaemia are identified. We have generated a mouse with a mutation in a gene called c-Cbl that promotes the activation a protein called FLT3 that is involved in the development of many types of leukaemias. By treating mutant mice a drug that specifically suppresses the function of FLT3 we intend to identify the most effective treatments for human leukaemias associated with activated forms of FLT3.Read moreRead less
The Microniche: A Novel In-vitro And In-vivo Prostate Cancer Model System
Funder
National Health and Medical Research Council
Funding Amount
$561,012.00
Summary
Maintaining primary prostate cancer cells (PCa) in vitro remains an enormous challenge for the field, and this obstructs efforts to systematically characterize cell behaviour and quantify drug response. Our group recently developed a 3-demsensional (3D) organoid culture system that does maintain PCa in vitro, and here we will integrate this technology with our 3D bone maorrow niche model system to better characterize PCa bone metastases and identify new clinical treatment regimes.
Linking Breast Development To Bone Metastasis: Role For The Osteogenic Transcription Factor Runx2 During Breast Carcinogenesis
Funder
National Health and Medical Research Council
Funding Amount
$565,145.00
Summary
Bone is the principle metastasis site of breast cancer and represents a major cause of morbidity and mortality. Runx2 is one potential candidate gene mediating breast cancer metastasis. Using mice with altered Runx2 levels and breast cancer models, this study will examine the role of Runx2 in breast cancer bone metastasis. Identification of a single gene that controls both breast and bone would open a new area of breast cancer research and a new gene against which therapies could be developed.
Targeting Bone Marrow Mediated Angiogenesis And Metastasis In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$463,006.00
Summary
Despite advances in treatment and diagnostics breast cancer (BC) remains one of the leading causes of death in women. Metastases and tumour blood vessel recruitment are linked. Work by Dr Mellick and others has shown that host bone marrow contributes endothelial progenitor cells (EPCs) to tumour vasculature. The chemokines and their receptors, which differentiate EPCs from tumour vessels, will be knocked down in the tumour cells and EPC progenitors with the aim of preventing tumour spread.
Roles Of Cascades Of Transforming Growth Factor-beta And Matrix Metalloproteinases In The Impact Of Cancer Stem Cells On The Neoplasm Formation Of Oral Squamous Cell Carcinoma.
Funder
National Health and Medical Research Council
Funding Amount
$81,793.00
Summary
Failure of treatment of oral cancer patients is because the specific cancer cells escape from chemo-radiotherapy. These cells feature self-renew and fast growth, which are called cancer stem cells (CSC). We will test our hypothesis “the genes of TGF-?1 and MMP initiate CSCs” using our cell-mouse models to arrest cancer progression, and verify the impact of CSC on cancer formation. This study is critical to know how to arrest CSC and offer an opportunity to develop a targeted anti-cancer therapy.
KLK4 Is A Master Regulator Of Tumour Microenvironment Remodelling In Prostate Cancer And Bone Metastasis
Funder
National Health and Medical Research Council
Funding Amount
$596,305.00
Summary
The current biomarker for prostate cancer, PSA, belongs to a large family of related proteins called KLK enzymes. We have evidence that one of these enzymes, KLK4, regulates many different pathways involved in tumour spreading especially to bones. This project will determine the specific components involved with a view to finding better biomarkers of tumour spread and bone metastasis and designing better treatments for these aspects of the disease.
Activating Transcription Factor 3 And Cancer Progression
Funder
National Health and Medical Research Council
Funding Amount
$767,794.00
Summary
We have shown that the transcription factor ATF3 suppresses bladder cancer spread. Turning off ATF3 is associated with disease progression in bladder and colorectal cancer. We will test whether levels of ATF3 can be used as a prognostic maker for disease progression, investigate the mechanisms underlying the actions of ATF3 in bladder and colorectal cancer and test whether therapeutically activating ATF3 can inhibit cancer progression.