The Role Of The M6P-IGF-II Receptor In Regulating Cellular Function
Funder
National Health and Medical Research Council
Funding Amount
$276,598.00
Summary
We will investigate if a cell surface protein that suppresses the growth of breast cancer cells is also able to reduce the cancer spreading to other organs. The part of the molecule required for this effect will be identified so that smaller forms of the protein can be tested to inhibit tumour spread. Genes and proteins altered by the presence of this protein in breast cancer cells will be examined to determine how the protein suppresses tumours and to identify novel tumour markers.
Tailored Treatments For Premenopausal Women With Endocrine Responsive Breast Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$299,213.00
Summary
For women <50yrs with ER+ breast cancer adjuvant treatment (AT) with chemotherapy (CT), tamoxifen and ovarian function suppression (OFS) are each effective and reduce recurrence. Combining 2 treatments is more effective than 1, but it is unclear if combining 3 provides any extra benefit. 2 trials,SOFT and TEXT, aim to answer this question. SOFT tests the benefit of adding OFS for very young women who remain premenopausal after CT, TEXT is for women who should receive OFS from the start of AT.
Development Of Modified IGF-binding Proteins As Novel Anti-cancer Chemotherapeutics
Funder
National Health and Medical Research Council
Funding Amount
$77,375.00
Summary
We propose to enhance the effectiveness of current anti-cancer treatments by co-administering a protein to sequester growth factors that promote the resistance of cancer cells to chemotherapy. We aim to achieve improved destruction of breast and colorectal cancers but with reduced adverse side effects. Our in vitro data show the effectiveness of this novel co-therapeutic which is a modified form of a natural carrier protein for these growth factors. This application seeks funding to enable proof ....We propose to enhance the effectiveness of current anti-cancer treatments by co-administering a protein to sequester growth factors that promote the resistance of cancer cells to chemotherapy. We aim to achieve improved destruction of breast and colorectal cancers but with reduced adverse side effects. Our in vitro data show the effectiveness of this novel co-therapeutic which is a modified form of a natural carrier protein for these growth factors. This application seeks funding to enable proof of concept in vivo in order to attract commercial funding for clinical trials.Read moreRead less
The Role Of Snail Family Proteins In Stem Cells And Tumour Growth
Funder
National Health and Medical Research Council
Funding Amount
$589,175.00
Summary
This project investigates the role of a family of genes in regulating stem cells in normal tissues and cancer. This family can switch other genes off and we hypothesize that keeping these genes off is required to allow stem cells to be maintained in tissues. We combine novel studies in fruit flies and mice to examine gene function in stem cells and tumour initiation. These studies will increase our knowledge of how to manipulate stem cells and may identify new targets for tumour therapy.
Analysis Of Gene Amplification-loss And Methylation Associated With Progression To Metastatic Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$620,197.00
Summary
Many bowel cancers can be removed by surgery, but in many cases the cancer reoccurs. While chemotherapy can reduce the chance of recurrence, it can produce significant side effects. Currently there are few markers to indicate change of recurrence, therefore deciding who should, or should not receive chemotherapy is difficult to decide. This study will analyse differences in DNA from patients that do and do not relapse, to guide future decisions on patients who will benefit from chemotherapy.
The Importance Of VEGF-D, An Angiogenic Protein, For Lymphangiogenesis, Tumor Growth And Metastasis.
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
Tumors attract blood vessels to obtain the nutrients for growth. Furthermore, the presence of blood vessels in a tumor enables tumor cells to enter the bloodstream and spread to distant parts of the body - a process known as metastatis that is the major cause of death in cancer patients. The growth of blood vessels - angiogenesis - is the mechanism by which tumors attract the vasculature. The capacity to block tumor angiogenesis would be of great benefit in the clinic as it would restrict both t ....Tumors attract blood vessels to obtain the nutrients for growth. Furthermore, the presence of blood vessels in a tumor enables tumor cells to enter the bloodstream and spread to distant parts of the body - a process known as metastatis that is the major cause of death in cancer patients. The growth of blood vessels - angiogenesis - is the mechanism by which tumors attract the vasculature. The capacity to block tumor angiogenesis would be of great benefit in the clinic as it would restrict both the growth and spread of tumors. Tumor cells attract blood vessels by secreting angiogenic growth factors that stimulate the proliferation of endothelial cells - the cells that form the inner lining of blood vessels. These Vascular Endothelial Growth Factors (VEGFs) are proteins. One VEGF, namely VEGF-D, was discovered in our laboratory at the Melbourne Branch of the Ludwig Institute for Cancer Research. VEGF-D stimulates the growth of blood vessels and possibly lymphatic vessels and is present in the most common human cancers including malignant melanoma and cancer of the breast and lung. We hypothesize that angiogenesis in some tumors is dependent on VEGF-D. Moreover, VEGF-D secreted by tumor cells may stimulate growth of lymphatic vessels - lymphangiogenesis. As metastatic spread often occurs via the lymphatic vessels, tumor lymphangiogenesis induced by VEGF-D may contribute to metastasis. The purpose of the research project is to determine the role of VEGF-D in tumor angiogenesis and lymphangiogenesis. Firstly we will thoroughly characterize the localization of VEGF-D in human cancer. Secondly, we will test VEGF-D for lymphangiogenic activity. Thirdly, the growth and metastatic spread in mice of tumors overexpressing VEGF-D will be analysed. Finally, aspects of VEGF-D biochemistry and gene regulation will be studied to develop strategies for inhibition of VEGF-D action in cancer.Read moreRead less
Development Of Anti-metastatic And Tumour Targeting Reagents By Design Of Inhibitors To Specific Eph/ephrin Cell-cell
Funder
National Health and Medical Research Council
Funding Amount
$200,000.00
Summary
Metastatic disease, malignant melanoma in particular, is a health issue of considerable global importance with 1,000 fatal melanoma cases- year in Australia alone. While progress has been made on prevention and early diagnosis, no curative treatment exists for stage IV melanoma. Tumour progression and the acquisition of metastatic competence primarily reflect dysregulation of cell adhesion and cell motility rather than proliferation and survival. In this context, Eph receptor tyrosine kinases (E ....Metastatic disease, malignant melanoma in particular, is a health issue of considerable global importance with 1,000 fatal melanoma cases- year in Australia alone. While progress has been made on prevention and early diagnosis, no curative treatment exists for stage IV melanoma. Tumour progression and the acquisition of metastatic competence primarily reflect dysregulation of cell adhesion and cell motility rather than proliferation and survival. In this context, Eph receptor tyrosine kinases (Ephs) and their membrane-bound ephrin ligands are crucial mediators of cell adhesion and motility and are notably overexpressed in metastatic tumours rather than primary (benign) lesions5. Our laboratories were the first to identify EphA3 7, and one of the first to isolate its ligand, ephrin-A5. EphA3 was isolated from acute lymphoblastoid leukemia and malignant melanoma patients, where increasing expression levels correlate with metastatic progression. Soluble, non-clustered forms of Ephs and ephrins are effective inhibitors of Eph activity 3 and provide opportunities to generate specific drugs for cancer therapy. We now propose a research and development program for the development of EphA3-specific drugs and their production for pre-clinical and clinical evaluation for placement onto a national and international market.Read moreRead less
Stage II In The Development Of Eph/ephrin Based Tumor Targeting Reagents: Optimisation Of Drug Efficacy And Delivery
Funder
National Health and Medical Research Council
Funding Amount
$204,125.00
Summary
In the final stage of cancer, including melanoma, tumor cells gain the ability to spread, a process called metastasis. Altered communication between cancer and normal cells is one of the causes of this invasive characteristic. We have started the development of novel agents that target and modulate proteins on the cell surface that control these properties and are found in metastatic tumors. We propose to refine the targeting and killing properties of these agents for early clinical testing.