A Single Nucleotide Resolution Map Of A Cancer Associated Neochromosome
Funder
National Health and Medical Research Council
Funding Amount
$567,350.00
Summary
Neochromosomes (NCs) are large chromosomes which are not usually found in a normal cell. Well differentiated liposarcoma (WDLPS) is a tumour which is almost universally associated with the presence of NCs. We are using the approach of purifying the NC from a series of WDLPS cell lines, and using new techniques to derive the DNA sequence of the neochromosome. We will use this information to identify the genetic factors on the NC which are involved in the initiation or progression of WDLPS.
Integrating Wnt-Apc Pathway With TGF-beta Signalling In Colon Cancer
Funder
National Health and Medical Research Council
Funding Amount
$342,364.00
Summary
Colon cancer is one of the leading causes of death of all cancers. Two molecular pathways have been independently implicated in colon cancer development. Emerging evidences suggest that the two pathways may work together in the colon polypus formation. This application will integrate two separate molecular causes to form a new coherent understanding of cancer development and offer new directions in development of novel colon cancer treatment.
Manipulating The B-RAF/MEK Pathway In The Genesis And Treatment Of Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$562,815.00
Summary
Melanoma is a major Australian health problem. It is the third most common cancer in men and women and has a disproportionately heavy impact on productive years of life. The use of small molecule inhibitors is the most promising strategy for treating melanoma. In this project, we will examine the mechanisms of resistance to this class of drugs and define new drug targets by examining the molecular-circuitry that is damaged in melanomas. This work will greatly accelerate the development of new th ....Melanoma is a major Australian health problem. It is the third most common cancer in men and women and has a disproportionately heavy impact on productive years of life. The use of small molecule inhibitors is the most promising strategy for treating melanoma. In this project, we will examine the mechanisms of resistance to this class of drugs and define new drug targets by examining the molecular-circuitry that is damaged in melanomas. This work will greatly accelerate the development of new therapies.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 Nature And Significance Of Clonal Evolution In Human Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$665,420.00
Summary
Cancers can progress in patients by developing genetic changes that favor the growth, survival and spread of cancer cells. However, the rate at which genetic changes occur in human cancer is not known. This project will determine the degree and biological significance of genetic change in human melanoma by using a novel method of growing tumors from single cells and comparing genetic differences between them.
Induction Of Senescence In Cells That Use The Alternative Lengthening Of Telomeres (ALT) Mechanism
Funder
National Health and Medical Research Council
Funding Amount
$474,048.00
Summary
Approximately 10-15% of all cancers depend on Alternative Lengthening of Telomeres (ALT) for their continuing growth. A key aspect of many successful cancer treatments is that they force cancer cells to undergo a form of permanent growth arrest called senescence. In this study we will investigate characteristics of ALT-positive cancer cells that may make them especially vulnerable to senescence. This may be exploited in the future as a therapeutic strategy for cancers that depend on ALT.
Understanding The Molecular Pathways That Determine Response To Anti-angiogenic Therapy
Funder
National Health and Medical Research Council
Funding Amount
$209,539.00
Summary
Anti-angiogenesis is an important new approach to treat conditions such as cancer and eye disease. Our study is designed to understand the molecular pathways that lead to patients either being or developing resistance to these treatments. Using advanced cell and molecular biology techniques we will identify ways in which the blood vessels evade these therapies. Once identified these molecules will provide additional targets for developing therapeutics and diagnostics.
Overweight individuals have an increased risk for developing liver cancer. This may be due to the reduced production of the fat-derived hormone adiponectin. Reduced levels of adiponectin are associated with increased inflammation and liver disease. Using mice not expressing adiponectin we will test its importance in liver cancer growth. The proposed research will provide a better understanding of the factors that promote liver cancer formation.
Defining Stromal-Cancer Cell Interactions For Xenografting Human Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$559,635.00
Summary
Prostate Cancer research continues to be hindered by a lack of laboratory models to understand disease progression and design new drugs to cure the disease. In this study, we propose to use a new and reliable method of growing human prostate cancer tissue in mice. Using this model, we will investigate the role of hormone signalling and cellular communication in prostate cancer that may lead to new therapies for men diagnosed with organ-confined disease.
Understanding The Role Of PI 3-kinase Mutations In Gastrointestinal Tumourigenesis
Funder
National Health and Medical Research Council
Funding Amount
$283,880.00
Summary
Mutations in the PIK3CA gene are frequently found in bowel cancers but it remains unclear exactly how these mutations are involved in cancer development. We will exploit a unique mouse model to explore the role of PIK3CA mutations in the initiation, progression and-or metastasis of gastrointestinal cancers. This work will provide critical new insights into the biology of PIK3CA mutations and lead to the development of better models for the testing of new anti-cancer therapies.