March is Myeloma Awareness Month
Myeloma, or multiple myeloma, is a type of blood cancer that develops in specific white blood cells, known as plasma cells. As plasma cells are produced in the bone marrow, found in the centre of larger bones, it can affect multiple places in the body – the spine, skull, pelvis, ribs, shoulders, and hips. In 2022, an estimated 2,600 people were diagnosed with multiple myeloma in Australia, according to the Australian Institute of Health and Welfare.
Dr Vasilios Panagopoulos is an early career cancer researcher at the South Australian Health and Medical Research Institute (SAHMRI) within the Myeloma Research Laboratory, University of Adelaide. One of his research interests is understanding the role of the tumour microenvironment in the progression of multiple myeloma and using this knowledge to identify new therapies to improve patient outcomes.
In 2023, Dr Panagopoulos is working on a project titled ‘Targeted inhibition of myeloperoxidase: a new therapeutic strategy to prevent multiple myeloma disease progression’, with the support of the Can Too Foundation, Cancer Australia, and the Leukaemia Foundation. The following is a brief overview of the project's importance, research plan, and anticipated impact.
Importance of the project
Currently, only three out of ten people with multiple myeloma will be alive ten years after their initial diagnosis. Dr Panagopoulos says that ‘one of the major concerns myeloma patients face as they endure numerous lines of therapy is that the efficacy and duration of disease response decreases with each subsequent round of treatment until patients become refractory to all treatment and unfortunately succumb to their disease’.
There is a real need for ‘the development of new, well-tolerated therapies to overcome treatment resistance and prevent patient's relapsing’. Dr Panagopoulos’ research focuses on developing a new treatment strategy to address this unmet clinical need.
‘The eradication of this currently incurable disease will, in part, depend on our understanding of the microenvironment of the bone marrow, the factors that play a role in supporting the growth and survival of this aggressive cancer, and the development of new therapies targeting these factors’, says Dr Panagopoulos.
‘Recent studies from our laboratory, and others, have highlighted the critical role of extrinsic factors within the tumour microenvironment as key regulators of immune evasion, disease progression and persistence. Therefore, developing new drugs that target factors from the tumour microenvironment in combination with standard-of-care anti-myeloma treatments may be more effective.’
Myeloperoxidase (MPO) is an enzyme involved in the immune response. It is used as a biomarker of inflammation in many diseases, including cancer, with reduced cancer risk associated with lower MPO expression. In preliminary experiments, Dr Panagopoulos and his team have shown increased MPO activity within the tumour microenvironment of mice with multiple myeloma. Their research also suggests that this ‘increased MPO activity can stimulate multiple myeloma tumour cell recruitment and growth within the bone marrow.’
These results make MPO a promising novel target for treating multiple myeloma, as inhibiting MPO activity may reduce tumour development. In collaboration with industry, Dr Panagopoulos will evaluate the therapeutic potential of an existing MPO inhibitor to treat multiple myeloma.
‘We will use our pre-clinical mouse models of multiple myeloma to determine the efficacy of the MPO inhibitor, alone and in combination with the existing frontline anti-myeloma drug, bortezomib, as a possible new treatment approach to block MPO and eradicate multiple myeloma tumour cells respectively’, says Dr Panagopoulos.
Additionally, ‘we will use our newly developed lenalidomide-sensitive mouse model to test whether the combination of the MPO inhibitor and lenalidomide can neutralise both MPO activity and the cells that release MPO, and consequently impede multiple myeloma progression.’
Through these experiments, Dr Panagopoulos hopes to ‘generate the crucial pre-clinical data required to support the translation of the MPO inhibitor into clinical trials for treating people with multiple myeloma’.
Anticipated impact of the project
In the short-term, the project will ‘increase our understanding of the mechanisms that underpin the role MPO plays in supporting myeloma development and whether MPO is an effective therapeutic target for the treatment of people with newly diagnosed multiple myeloma in combination with standard-of-care anti-myeloma agent bortezomib’. While in the long-term, ‘the ultimate aim is the inclusion of MPO inhibitors as a new treatment approach in multiple myeloma, and ultimately to improve patient outcomes.’
Want more information?
Further information on Can Too funded researchers, including Dr Vasilios Panagopoulos, and multiple myeloma can be found at:
Data on the incidence of multiple myeloma in Australia was obtained from the Australian Institute of Health and Welfare, Cancer Data in Australia Web Report, AIHW Website, accessed 20 March 2023.
Author: Trish Dwight
Date: 28 March 2023