Deciphering Breast Cancer Heterogeneity To Improve Breast Cancer Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$851,980.00
Summary
Breast cancer is a very heterogeneous disease. Patients are often treated in a ‘one size fits all’ approach, but response to therapy remains quite disparate. To better personalise therapy, there is a pressing need to define the precise cell types and initiating genetic events that give rise to breast cancer. This application is focussed on understanding the molecular and cellular origins of breast cancer, with the potential of identifying new prognostic markers and therapeutic targets.
Prof Lindeman's laboratory, co-headed with Dr Visvader, has played an influential role in the identification of mammary stem and progenitor cells, elucidation of the mammary epithelial cell hierarchy and gaining insights into how female hormones regulate mammary gland development and cancer. In parallel, I have established translational research platforms such as patient-derived tumour xenograft (PDX) models, which offer powerful preclinical models to test new drugs.
Elucidating The In Vivo Role Of The Pro-survival Gene Mcl-1 In Mammary Gland Development And Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$664,691.00
Summary
Breast cancer strikes one in 8 women by age 85 and is a major cause of morbidity and mortality. Despite recent improvements, the immense breast cancer burden demands new strategies that will radically improve patient outcomes. This project will address a hallmark of cancer: evasion of apoptosis. Understanding the molecular events that promote tumour survival and resistance to therapy represents a key area in cancer biology that has yet to be properly applied to breast cancer.
Cell Survival Pathways As Potential Targets In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$142,914.00
Summary
Cancer cells are characterised by their capacity for relentless growth, survival and evasion of cell death. This proposal will use patient derived xenograft models of primary breast cancer to test the hypothesis that addition of BH3-mimetics could improve response to anti-HER2 therapy. This technique involves transplantation of patient tumours into immune-compromised mice. This represents a useful method for testing new agents.
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.
Determination Of The Cellular Origins Of Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$705,563.00
Summary
Breast cancer is a highly heterogeneous disease with multiple molecular and histological subtypes. We propose to use novel genetically engineered mice to understand breast inter-tumoral heterogeneity by dissecting the cells of origin of breast cancer in vivo. Initially, we will examine whether long-lived stem or progenitor cells are the targets of breast carcinogenesis induced by a progesterone derivative using our state-of-the-art multi-coloured reporter models to track the cells in vivo.
Apoptosis And Stem Cells In Cancer Development And Therapy
Funder
National Health and Medical Research Council
Funding Amount
$22,852,198.00
Summary
To improve cancer therapy, we are studying two cancer hallmarks: enhanced cell survival and stem cell-like behaviour. As we discovered, cell death is often blocked in cancer cells. Hence, we are attempting to develop drugs that flip the natural ‘cell death switch’. Stem cells are rare cells that generate entire tissues, as we showed for the breast. Certain cancers may be driven by ‘rogue’ stem cells. If so, eradication of these rare cells within the bulk tumour may require novel therapies.
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.
Functional Studies On The Role Of DNp73 In Stem Cells And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$428,838.00
Summary
This project investigates the role of the p73 gene in regulating stem cells and facilitating intestinal cancer formation. We hypothesize that when a particular form of this gene (DNp73) is upregulated it prevents differentiation of stem cells and promotes tumour formation. We combine novel approaches in mice and fruit flies to examine the function of DNp73 in stem cells with analysis of human tumour samples. These studies may identify a new target for tumour therapy.