Osteosarcoma is the most common cancer of bone. It osurs most frequently in childhood (teenage years) and current therapy is limited to surgery and chemotherapy. We have developed a new model of osteosarcoma that displays a high degree of similarity to human osteosarcoma. We aim to further understand this model and apply these findings to help treat human osteosarcoma.
The Role Of The Human RECK Protein In Modifying Human Sarcoma Progression Within In Vitro And In Vivo Models
Funder
National Health and Medical Research Council
Funding Amount
$34,878.00
Summary
The protein “RECK” is known to have a controlling effect on cancers by reducing growth, invasion, and blood supply. RECK is present in normal tissues but in bone and soft-tissue tumours (sarcomas), the protein is reduced. This study aims to; correlate RECK levels in sarcoma with patient survival, use gene technology to increase RECK levels in sarcoma cells, and observe the effects on sarcoma invasion and metastasis.
Molecular Mechanisms That Mediate The Anti-osteosarcoma Properties Of Pigment Epithelium-derived Factor (PEDF)
Funder
National Health and Medical Research Council
Funding Amount
$123,453.00
Summary
Cancer results from a sequence of alterations to genes which lead to abnormal cells dividing without control. Osteosarcoma is a cancer involving bone and can rapidly spread to surrounding and distant tissues. A number of mediators have been identified as being able to provide some regulation of this abnormal cell division. Pigment epithelium-derived factor is one such protein and further understanding of how it achieves this could be used for the development of targeted osteosarcoma treatment.
Characterisation And Therapeutic Targeting Of Molecular Pathways That Promote Breast Cancer Metastasis To Bone
Funder
National Health and Medical Research Council
Funding Amount
$442,573.00
Summary
Breast cancer that has spread to bone cannot be cured. Using the most clinically relevant model of breast cancer available we have identified that tumour cells growing in bone need to suppress immune elimination (by suppressing the Type I interferons) and invade through the bone tissue (by activation of cysteine cathepsins). Studying the functional role of these pathways will provide novel insight into the mechanisms of breast cancer spread to bone that can be augmented therapeutically.
MMP13 is upregulated in cancer cells and in the tissue that forms around the cancer (stroma). A new MMP13-specific inhibitor reduces breast cancer growth in a mouse model, both at the primary site and also in bone. We will determine the role of MMP13 made by the cancer cells and stroma, respectively, extend the inhibitor work, and identify proteins being cleaved by MMP13. Being a late-stage manifestation, bone metastasis may represent an important clinical trial setting for MMP inhibitors.
Acute myeloid leukaemia (AML) is a major health problem with only about one third of patients being cured. In addition therapies have changed little over the last 20 years. However there is optimism that with greater knowledge of the biochemical changes in AML that are caused by genetic mutations, more effective treatments will be developed. This project therefore aims to increase understanding of the biochemical interplay between two proteins called c-Cbl and Flt3 that are altered in AML.
Mechanism Of Breast Cancer Metastasis: Tumour Cell Remodelling Of The Extracellular Matrix
Funder
National Health and Medical Research Council
Funding Amount
$377,331.00
Summary
The main complication in breast cancers leading to death is metastatic relapse. This research aims to understand the role for a protease that promotes spread of breast cancer to the lymph nodes and lungs. The outcomes will identify a novel process that leads to lymph node metastasis and offer a new target for therapies that prevent relapse and tests to identify breast cancer patients at risk of relapse.
Activated Dendritic Cell Monoclonal Antibodies As Therapeutics To Prevent Graft Versus Host Disease
Funder
National Health and Medical Research Council
Funding Amount
$432,750.00
Summary
A New Therapy to Prevent Graft versus Host Disease in Bone Marrow Transplantation Bone marrow transplants often fail due to the immune reaction of the grafted donor cells against the patient (graft versus host disease). Current treatments to prevent this do not always work and have serious side-effects or other disadvantages.The immune reaction is induced by activated dendritic cells which are the primary stimulators of the body's defences against foreign invaders. We have developed antibodies i ....A New Therapy to Prevent Graft versus Host Disease in Bone Marrow Transplantation Bone marrow transplants often fail due to the immune reaction of the grafted donor cells against the patient (graft versus host disease). Current treatments to prevent this do not always work and have serious side-effects or other disadvantages.The immune reaction is induced by activated dendritic cells which are the primary stimulators of the body's defences against foreign invaders. We have developed antibodies in mice that react with human activated dendritic cells and prevent them from inducing immune responses in the test-tube. These antibodies are also likely to be effective in patients, but cannot be used in their present form because mouse antibodies induce an undesirable immune response in humans. We therefore plan to convert them to resemble human antibodies (antibody engineering). Antibodies that react with other types of cell in the body are already used to treat or prevent a variety of conditions, including graft versus host disease, but no one has developed a therapeutic antibody against activated dendritic cells. We are applying to the NHMRC for funding to engineer our antibodies and to test them in test tube experiments and also in mouse models of graft versus host disease. We also plan to study the changes in blood levels of activated dendritic cells in bone marrow transplnt patients. This will provide information on the best time to use our new therapeutic antibodies to prevent graft versus host disease. The aim of this grant application will have been achieved if, after three years, we have a new antibody ready for testing in bone marrow transplant patients.Read moreRead less
Role Of A Novel Tks5-Nck Signaling Pathway In Cancer Invasion
Funder
National Health and Medical Research Council
Funding Amount
$560,434.00
Summary
Invasion and metastasis are major causes of death in cancer patients. Our research has uncovered a pathway that increases the invasive potential of tumour cells in vitro. We now aim to determine if the pathway is relevant in invasion and metastasis in clinically relevant models; how a drug targeting the pathway affects invasion and; the extent to which the pathway is active in human tumours. These studies may identify a new molecular target for anti-invasive drugs.