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.
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.
Targeting Bone Marrow Mediated Angiogenesis And Metastasis In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$463,006.00
Summary
Despite advances in treatment and diagnostics breast cancer (BC) remains one of the leading causes of death in women. Metastases and tumour blood vessel recruitment are linked. Work by Dr Mellick and others has shown that host bone marrow contributes endothelial progenitor cells (EPCs) to tumour vasculature. The chemokines and their receptors, which differentiate EPCs from tumour vessels, will be knocked down in the tumour cells and EPC progenitors with the aim of preventing tumour spread.
Alpha-particles linked to recombinant antibodies targeting tumour cells have potential to effectively treat tumours while minimising normal tissue side effects. We will explore a novel alpha-particle therapy approach to solid tumours, by delivering 225Ac directly into tumour cells, or into cells that support the tumour (microenvironment). This approach will hopefully result in development of a new approach to treatment of cancers that are resistant to conventional therapies.
Targeting Microtubules To Overcome Chemoresistance In Pancreatic Cancer
Funder
National Health and Medical Research Council
Funding Amount
$594,336.00
Summary
Pancreatic cancer is a devastating disease with a dismal prognosis because it is extremely resistant to chemotherapy agents. We plan to examine the expression of proteins called microtubules in pancreatic cancer and assess their role in drug resistance. It is anticipated that the findings of these studies will lead to the development of effective approaches to sensitise the cancer cells to chemotherapy agents.
Targeting Tumour-Stromal Interactions In Pancreatic Cancer
Funder
National Health and Medical Research Council
Funding Amount
$410,095.00
Summary
Pancreatic cancer claims five Australian lives every day and is one of the nations most lethal diseases. Despite aggressive treatment regimes, there has been no improvement in patient survival in the last decade. Evidence suggests that targeting cancer cells alone is not enough. The intense stromal reaction inhibits drug delivery and increases the aggressiveness of the tumours. Thus, depletion of the stroma or pancreatic stellate cells is a potential therapeutic target.
GENETIC PREDICTION OF FRACTURE IN A RISK-STRATIFIED POPULATION
Funder
National Health and Medical Research Council
Funding Amount
$363,000.00
Summary
Osteoporosis is a condition characterised by excessive bone loss and impaired bone quality, which ultimately results in fracture with minimal trauma. Osteoporosis affects 27% of women and 11% of men aged 60 years or above in the community, and costs Australia around $7 billion each year. Individuals with low bone mineral density (BMD) have a significantly higher risk of fracture than those with normal BMD. In the long-term (14-year) Dubbo Osteoporosis Epidemiology Study, more than half of indivi ....Osteoporosis is a condition characterised by excessive bone loss and impaired bone quality, which ultimately results in fracture with minimal trauma. Osteoporosis affects 27% of women and 11% of men aged 60 years or above in the community, and costs Australia around $7 billion each year. Individuals with low bone mineral density (BMD) have a significantly higher risk of fracture than those with normal BMD. In the long-term (14-year) Dubbo Osteoporosis Epidemiology Study, more than half of individuals with osteoporosis (e.g., low BMD) did not sustain a fracture, while approximately 60% of fracture cases had BMD above the high risk levels. Thus, BMD alone is not a good discriminant of fracture versus non-fracture cases. It is widely known that the liability to fracture is determined in part by genes. Previous studies, including from our group, have suggested a number of candidate genes that are associated with fracture risk. The fundamental issue that this study is concerned is that how and whether genetic markers could be used to facilitate case finding. It is proposed that common variations of certain genes are associated with fracture risk independent of BMD. That is, they can identify individuals at relatively high and low fracture risk after stratification for BMD. Hence, some markers may identify those individuals likely (and unlikely) to fracture even with low (osteoporotic) BMD. Similarly, some, possibly the same, markers may identify individuals at high risk of fracture despite relatively good (ie non-osteoporotic) BMD. It is further proposed that no single gene will achieve this outcome, but rather a small set of such gene polymorphisms will provide clinically useful risk information. This effect is entirely analogous to the use of clinical risk indicators (eg, age, weight, sex, family history, etc) to assess the risk of future fracture.Read moreRead less
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.
This study aims to elucidate central pathways which can be manipulated to drive the storage of excess energy away from fat and instead directing it into the production of bone mass. Having identified leptin-responsive NPY neurons as important in the control of energy partitioning, we will focus on manipulating these neurons in the hypothalamus using innovative technology to alter body composition. This research has the potential to result in novel treatments for obesity and osteoporosis.