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Long-term In Vivo Imaging Of Bone Marrow Microenvironments In Multiple Myeloma.
Funder
National Health and Medical Research Council
Funding Amount
$688,371.00
Summary
White blood cells are soldiers of the immune system. When the machinery that controls growth and death of these cells is disrupted, these cells can undergo massive expansion. This leads to the development of blood cancers such as multiple myeloma (MM). In MM, malignant cells infiltrate bones preventing production of blood and damaging the bone structure leading to fractures. Using cutting edge microcopy we will watch how MM cells grow and damage bone tissue to develop new therapeutic approaches.
The Role Of NK Cell Receptors In Tumor Immunity And Cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$641,264.00
Summary
White blood cells lymphocytes have an important role to play in cancer immunity and the activity of some cancer therapies. Therapeutics that improve lymphocyte function in patient tumors are showing great promise. Yet, virtually nothing is known about one family of lymphocyte receptors that control function in cancer. Using relevant mouse models of cancer and patient tumors we now wish to assess the relative importance of this family of receptors in tumor immunity, therapy, and escape.
Why Is The Bone Marrow A “hot-spot” For Myeloma Plasma Cell Metastasis: Are There Gremlins In The System?
Funder
National Health and Medical Research Council
Funding Amount
$651,979.00
Summary
Most cancer patients die because their cancer spreads from a primary site to other tissues in the body. Once escaping the primary site, 70% of all tumours will spread to bone. This raises the question, why is bone a preferred destination for cancer cells? We provide evidence that Gremlin1, made by non-cancer cells within bone, is a key protein that supports cancer growth. This study will examine whether inhibiting Gremlin1 is a potential therapy to inhibit cancer spreading to bone.
Analysis Of Circulating Tumour DNA For Mutational Characterisation And Tracking Disease Progression In Multiple Myeloma
Funder
National Health and Medical Research Council
Funding Amount
$908,676.00
Summary
Multiple myeloma is cancer of plasma cells in the bone marrow and presents at multiple sites with dissimilar genetic information (GI) across these sites. Invasive biopsies of multiple sites are required to determine the GI. Cancer cells shed small amounts of DNA into the blood stream and this circulating DNA (ctDNA) contains GI from multiple cancer sites. This project will evaluate the utility of ctDNA to determine GI and to predict treatment response in MM patients.
Myeloma Plasma Cell Dormancy - 'Eradicating The Sleeping Giant'
Funder
National Health and Medical Research Council
Funding Amount
$834,428.00
Summary
Multiple myeloma is a fatal cancer that develops in the skeleton. Current therapies are initially effective, but patients develop resistance and the disease returns. This makes the search for drugs to overcome resistance a priority. Myeloma cells can hide in bone in a dormant state where they are insensitive to chemotherapy. We have identified new drug targets in dormant cells. We are investigating whether these new targets can be used eradicate myeloma cells and cure the disease.
A Genomic Approach Towards An Understanding Of Clonal Evolution And Disease Progression In Multiple Myeloma
Funder
National Health and Medical Research Council
Funding Amount
$671,689.00
Summary
Cancer development is associated with changes in the genetic composition of the cell. These changes involve the loss/gain of genetic material and/or changes in gene expression. Using sophisticated technology, we will define the changes in the genes that are associated with the transition from a benign to a malignant cancer state. We will examine this process in the blood cancer, multiple myeloma, in order to identify new treatment targets for this incurable disease.
Molecular & Translational Characterisation Of IMiD-Mediated BET-Protein Degradation In Multiple Myeloma
Funder
National Health and Medical Research Council
Funding Amount
$497,857.00
Summary
Thalidomide-like drugs (called IMiDs) are an essential treatment for multiple myeloma, a common incurable blood cancer. We have discovered that IMiDs destroy proteins that myeloma cells use to ‘read’ cancer-causing genes in their own DNA. We will therefore investigate how important the destruction of these ‘gene readers’ is in myeloma cells, including patient samples. This will set up future studies targeting ‘gene readers’ using IMiDs in combination with other targeted drugs in clinical trials.
Does Teriparatide Reverse Osteonecrosis Of The Jaw In Patients With Cancer? A Randomised, Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$357,412.00
Summary
Osteonecrosis of the jaw (ONJ) is debilitating and associated with drugs that increase bone strength and reduce the bone remodeling rate (bisphosphonates or denosumab). Up to 15% of patients with bone marrow cancer and 1 out of 952 patients with osteoporosis treated with bisphosphonates may get ONJ. This 8-week trial of subcutaneous teriparatide (a hormone that forms new bone) or placebo injections aims to promote resolution of ONJ, measured clinically and by x-ray, and improve quality of life.
Determining The Essential Regulators Of Antibody Production
Funder
National Health and Medical Research Council
Funding Amount
$768,612.00
Summary
Plasma cells produce the antibodies that are essential to protect us from pathogenic microorganisms and provide the basis for the beneficial effects of vaccination. Plasma cells can also cause disease through the production of antibodies against our own body, for example in Lupus and in the blood cell cancer multiple myeloma . Our research aims to understand the genetic regulation of antibody production, with an aim to "switch off" inappropriate antibody supply in disease.
Bone Marrow Macrophages: “Resident Evil” In The Establishment And Progression Of Multiple Myeloma
Funder
National Health and Medical Research Council
Funding Amount
$570,585.00
Summary
Multiple myeloma (MM) is a cancer that develops within the bone marrow (BM). To date, which cells of the BM stroma are required for the support of MM growth remains unknown. Our preliminary data suggest BM resident macrophages, expressing CD169 and CX3CR1, are essential for MM growth. Using innovative and elegant animal models of MM, we will define the role of these macrophages in MM growth and determine if macrophage-targeted therapies can delay MM growth in the relapsed disease setting.