Role Of The Inositol Polyphosphate 4-phosphatase Type 2 In Human Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$611,032.00
Summary
Breast cancer is the most invasive cancer in females, affecting 1 in 9 women before the age of 85. Normally cells only divide when they receive a stimulus from a hormone or growth factor. The PI3K pathway responds to these stimuli and has been implicated in cancer when cells divide uncontrollably and invade surrounding tissue. We have identified a potential cancer suppressing gene, 4-ptase-2 that turns off the PI3K growth signals. We aim to characterize the role of 4-ptase-2 in breast cancer.
Epigenetics describes how genes can be turned off or on without changing the DNA sequence. Epigenetics plays a major role in cancer development. In this proposal we are investigating a novel hypothesis that in cancer a similar mechanism to imprinting USING NON-CODING RNA is triggered and this promotes the suppression of clusters of genes. The results from this proposal will have major implications to our understanding of gene regulation in cancer and will have important therapeutic value for can ....Epigenetics describes how genes can be turned off or on without changing the DNA sequence. Epigenetics plays a major role in cancer development. In this proposal we are investigating a novel hypothesis that in cancer a similar mechanism to imprinting USING NON-CODING RNA is triggered and this promotes the suppression of clusters of genes. The results from this proposal will have major implications to our understanding of gene regulation in cancer and will have important therapeutic value for cancer treatment.Read moreRead less
Studies On The Tumour-associated PIK3CA(H1047R) Mutation Using In Vitro And In Vivo Models Of Breast And Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$583,312.00
Summary
PIK3CA mutations are frequently found in breast and ovarian cancers but how they cause cancer is not clear. We will exploit a unique mouse model to investigate the functional effects of PIK3CA mutations in cells and their role in cancer development. Understanding the mechanisms by which PIK3CA mutations regulate cell function and drive tumour growth will allow the rationale design of novel anti-cancer agents that specifically target this important cancer pathway.
The Role Of ILK In Hedgehog Signaling And Medulloblastoma.
Funder
National Health and Medical Research Council
Funding Amount
$452,248.00
Summary
Molecular signaling pathways regulate normal embryo development, and deregulated signaling by these pathways causes many cancers. Hedgehog (Hh) is a signalling pathway commonly activated by mutations in specific genes to cause cancer, including medulloblastoma, the most common brain tumour of childhood. We have discovered novel protein interactions in the Hh pathway, and will use animal models of Hh-dependent medulloblastoma to investigate new anti-cancer drugs targetting these proteins.
The Pez-TGFbeta-miR200-ZEB1-2 Axis In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$533,541.00
Summary
A feature of late-stage cancer is metastasis - the dissemination of cancer cells to other tissues. Despite advances in treatment of primary cancers, metastatic disease remains the major cause of death in cancer patients. In metastatic cancers, the cells undergo a change that enables them to initially invade the surrounding tissues. We have discovered a novel regulator of the invasive process in tissue culture and this study aims to substantiate its role in breast cancer.
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.
It is seldom the initial cancer that kills the patient; most deaths are due to its metastatic spread throughout the body. Survival after the onset of a brain metastasis is dismal. Current understanding of cancer spread to the brain is poor and yet an ability to inhibit this process would save thousands of lives each year. Using rare tissue resources and cutting-edge technologies, this project will elucidate molecular features of brain metastases that can be exploited to generate new treatments.
Telomere Structural Abnormalities In Cells Using Alternative Lengthening Of Telomeres
Funder
National Health and Medical Research Council
Funding Amount
$522,122.00
Summary
The continuing growth of cancers depends on their cells being able to prevent shortening of chromosome ends (telomeres). Some cancers, including very aggressive brain and connective tissue tumours, achieve this via the Alternative Lengthening of Telomeres (ALT) process. We have evidence that the telomere structure of normal cells prevents ALT. Here we will examine how the telomere structure of ALT-positive cancer cells is changed, and whether reversing these changes inhibits ALT.
Mechanistic And Functional Characterization Of The Atypical Kinase SgK269
Funder
National Health and Medical Research Council
Funding Amount
$271,879.00
Summary
The overall aim of this study is to characterize at a mechanistic and functional level the oncogenic role of SgK269. We will use quantitative proteomics and phosphoproteomics to characterize the signaling network role of SgK269 and subsequently undertake a detailed structure/function analysis of SgK269 in mammary epithelial cells. Our study will provide novel insights into the signaling mechanism and function of SgK269 and highlight the potential strategies for improved treatment of basal breast ....The overall aim of this study is to characterize at a mechanistic and functional level the oncogenic role of SgK269. We will use quantitative proteomics and phosphoproteomics to characterize the signaling network role of SgK269 and subsequently undertake a detailed structure/function analysis of SgK269 in mammary epithelial cells. Our study will provide novel insights into the signaling mechanism and function of SgK269 and highlight the potential strategies for improved treatment of basal breast cancers.Read moreRead less
Molecular Characterisation Of Telomere Trimming And Its Role In Cell Proliferative Capacity
Funder
National Health and Medical Research Council
Funding Amount
$403,439.00
Summary
Telomeres are protective structures at the ends of chromosomes. Telomere length is a major determinant of how many times a cell can proliferate. We have recently discovered a rapid telomere shortening process that we have called telomere trimming. We will analyse the molecular details of this process to determine whether it could be used to shorten telomeres and stop cancer cell proliferation, and whether blocking it could increase cell proliferation in patients with short telomere syndromes.