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.
The behaviour of prostate cancer cells is regulated by their surrounding environment known as the stroma. The stroma has been proposed as a therapeutic target, but it is a diverse mix of cells that needs to be specifically targeted. Not all stromal cells are equal; cells surrounding tumours have different features from cells in normal tissue. Therefore, the goal of this project is to directly isolate cancer-associated stromal cells from patient tissue and study their role in cancer progression.
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.
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.
Uncovering The Role Of Collecting Lymphatic Vessels In Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$688,875.00
Summary
Lymphatic vessels are a critical part of the circulatory system, allowing the return of fluid and cells that escape the blood vessels, and playing an intimate role in the body's immune function. In cancer, the lymphatic vessels serve as conduits for the transport of tumour cells to lymph nodes and may contribute to distant metastasis. Our study is designed to understand the role played by major collecting lymphatic vessels in cancer and to identify molecules that control their activity.
Apoptosis And Stem/Progenitor Cells In The Development And Treatment Of Cancer
Funder
National Health and Medical Research Council
Funding Amount
$21,809,604.00
Summary
To improve cancer therapy, we are studying two cancer hallmarks. The first is excessive cell survival. To combat this, we are developing drugs with commercial partners that directly activate the cell's death machinery. The second hallmark is inexorable proliferation, akin to that of stem cells, which can generate entire tissues, as we showed for the breast. ‘Rogue’ stem-like cells may initiate certain cancers. We hope to advance cancer therapy by identifying such cells and drugs that kill them.