Myeloma Research Group

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Myeloma Research Group, Division of Blood Cancers

Goal

To identify better therapeutic strategies for the treatment of multiple myeloma (MM).

About us

The MRG within the Division of Blood Cancers, ACBD, focuses on the pre-clinical development of novel therapeutic agents for multiple myeloma and the identification of new therapeutic targets through the study of disease resistance and disease progression mechanisms. Recent work has discovered that dysregulation of the NOTCH signaling pathway promotes a more malignant phenotype with features of ‘epithelial to mesenchymal transition’ that may provide a unique therapeutic approach for drug sensitization utilizing NOTCH inhibition. In addition, recent work with small molecule inhibitors targeting HSP90, JAK and MEK have informed the design of in-house clinical trials for relapsed myeloma patients. The group utilizes a wide range of myeloma cell lines, including unique cell lines propagated in-house, and has extensive experience in the procurement of primary myeloma tumour cells for biological studies and drug testing. In vivo studies involve the use of the 5T33 syngeneic murine model of systemic myelomatosis and a recently established human-murine xenograft in NSG mice. The MRG works in close collaboration with the Haematology CRU undertaking focused correlative studies with a particular emphasis on biomarker recognition and development.

Research Focus and Tools

• The role of CD45 and EMT in MM disease progression
• Optimisation of epigenetic modifiers in MM therapy
• Heat shock proteins in MM
• 5T33 and NSG mouse models of MM
• Ex vivo primary MM cell drug evaluation

Research Overview

Multiple Myeloma (MM) is an incurable malignancy of terminally differentiated B-cells characterised by a high level of de novo drug resistance and a remitting relapsing clinical course. The MRG is focused on the mechanisms underlying de novo MM cell drug resistance; the processes that drive acquired drug resistance with disease progression; and, the identification and optimisation of novel therapeutic strategies for MM.

Projects and Opportunities

• Determining the mechanisms of action of de-acetylase inhibitors in MM
• Sirtuin dysregulation and role in MM
• Identification of biomarkers of novel drug responsiveness in MM
• Tumour heterogeneity in MM as a mechanism of drug resistance
• Loss of MM cell CD45 expression as a model of disease progression
• Testing novel drug combinations against primary MM cells and mouse models
• Heat shock proteins in MM

For current project opportunity descriptions please visit our honours page.

Selected Publications

Dawson M, Opat S, Taouk Y, Donovan M, Monaghan K, Horvath N, Roberts A, Prince HM, Hertzberg M, McLean C, Spencer A. Clinical and immunohistochemical features associated with response to bortezomib in patients with multiple myeloma. Clinical Cancer Research 2009; 15: 714-722. (IF 7.34)

Mithraprabhu S, Grigoriadis G, Khong T, Spencer A. De-acetylase inhibition in myeloproliferative neoplasms. Investigational New Drugs 2010; 28: 50-57. (IF 3.01)

Monaghan K, Khong T, Spencer A. The novel JAK2 inhibitor CYT387 suppresses multiple signalling pathways, prevents proliferation and induces apoptosis in phenotypically diverse myeloma cells. Leukemia 2011; 25: 1891-1899. (IF 8.97)

Khong T & Spencer A. Targeting HSP90 induces apoptosis and inhibits critical survival and proliferation pathways in multiple myeloma. Molecular Cancer Therapeutics 2011; 10(10); 1909-1917. (IF 5.26)