Does modifying the bone marrow stromal microenvironment alter the disease course of multiple myeloma?
Multiple myeloma (MM) is an incurable haematological malignancy characterised by the increased production (clonal proliferation) of malignant plasma cells (PCs) in the bone marrow. Each year, approximately 1,400 Australians are diagnosed with Multiple myeloma and alarmingly, over the last 25 years the incidence of Multiple myeloma has increased by 44%. Despite recent therapeutic advances, only modest improvements in overall patient survival have been achieved. It has become increasingly clear that successful anti- Multiple myeloma therapies must acknowledge the role played by the bone marrow microenvironment in this disease, and not just target the tumour cells. We are examining how bone marrow changes in response to Multiple myeloma tumour growth and whether changing the bone marrow environment can affect tumour establishment and growth. We propose that these studies will provide valuable insight into the therapeutic potential of current and future anti- Multiple myeloma strategies. Furthermore, these studies may also reveal mechanisms which have relevance to other haematological malignancies (blood and bone marrow cancers).
What we aim to achieve
While the research is “discovery-based” science, it may provide insight as to whether targeting the bone marrow microenvironment in patients who have the precursor condition to Multiple myeloma (mononclonal gammopathy of uncertain significance (MGUS)) may limit the transition from MGUS to active Multiple myeloma disease.
We aim to conduct genetic analysis of MSCs (Mesenchymal Stem Cells), cells which can turn into bone cells (osteoblasts), recovered from MM, MGUS and healthy donors. This will lead to a better understanding of how MM plasma cells affect MSC gene expression. This may identify existing and new pathways for MSCs which are intrinsically altered in response to malignant plasma cell exposure.
Ultimately, these studies will provide a better understanding of the pathophysiology of bone cell (osteoblasts) suppression in MM and may identify new therapeutic targets.
Our next steps and milestones
Our next steps are to use a model of myeloma to test agents, which may alter the bone marrow microenvironment and in turn, limit the progression of the disease.
What motivates me
I am motivated to meet the present and future health challenges that cancer presents to our community, while mentoring the next generation of cancer researchers.
My message to supporters
Despite recent therapeutic advances, only modest improvements in overall myeloma patient survival have been achieved. It has become increasingly clear that successful anti-MM therapies must acknowledge the role played by the BM microenvironment in this disease, and not just target the tumour cells. Funding from Cancer Council SA enables us to develop novel treatment strategies to better the health outcomes for patients with myeloma.