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.
Single Cell Genetic Profiling To Reveal Molecular And Cellular Changes In BRCA Preneoplastic Tissue
Funder
National Health and Medical Research Council
Funding Amount
$202,959.00
Summary
The initial molecular and cellular events that lead to breast cancer in women with BRCA1 or BRCA2 mutations are unknown. We will use state-of-the-art genomic tools (Single Cell RNA-seq and whole genome sequencing) to determine how cancer begins in absence of normal BRCA genes. Single cell genomic profiling of stem and daughter cells from pre-cancerous breast tissue will be used to identify early-indicator molecular changes that could be exploited in the clinic.
Targeting Cancer-initiating Cells With DNA Methyltransferase Inhibitors: Single-cell Analysis To Decipher Molecular Mechanisms And Improve Efficacy.
Funder
National Health and Medical Research Council
Funding Amount
$175,000.00
Summary
Certain cancer cells, termed cancer-initiating cells (CICs), have special properties allowing them to drive cancer growth and disease progression. These cells are particularly sensitive to low-dose treatment with drugs called DNA methyltransferase inhibitors. Using cutting-edge "single-cell" technologies this project will determine how these drugs target CICs and identify new ways to increase treatment efficacy. This work will identify new clinical opportunities for prevention of cancer relapse.
Defining The Role Of Reserve Stem Cells In Gastric Cancer
Funder
National Health and Medical Research Council
Funding Amount
$563,739.00
Summary
Over 800,000 deaths from stomach cancer occur annually. This often fatal disease is caused by chronic inflammation of the stomach lining. This proposal will investigate how stomach inflammation ‘reprograms’ a new type of 'cancer stem cell' to form tumours and evaluate ways to therapeutically target these cells to prevent disease. Collectively, these studies will inform new approaches for stomach cancer prevention and treatment.
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.
How Does The Tumour Suppressor: Nerfin-1 Prevent Dietary Dependent Tumour Growth?
Funder
National Health and Medical Research Council
Funding Amount
$630,942.00
Summary
The influence of diet has been linked to tumour growth for decades, however, there is little scientific evidence to support or disprove this. In this study, we will assess the effect of diet on tumours in fruit flies. The metabolic genes which regulate the growth of fly tumours will then be studied in human brain tumours. Our studies will ultimately shed light on how tissue growth is controlled by dietary intake, and have the potential to inform the way that we treat and manage human cancers.