Hepatocyte Growth Factor (HGF)-signalling as target for treatment of multiple myeloma

Multiple myeloma is due to clonal expansion of malignant plasma cells. The incidence in the Nordic countries is approximately 6 new cases per 100,000 per year, which corresponds to nearly 20% of hematological cancers. Approximately 300 persons are given t his diagnosis each year in Norway. An important property of multiple myeloma is its unique localization to the bone marrow, indicating that the bone marrow microenvironment has distinctive features that are essential for the growth and survival of the mal ignant plasma cells. In almost all patients, the neoplastic clones induce osteoclast activity, resulting in osteoporosis, osteolytic lesions and pathological bone fractures. The bone disease of multiple myeloma represents a serious complication and is of ten associated with pain and severely reduced quality of life. Multiple myeloma is still an incurable disease. It is likely that new and better treatments will emerge from a better understanding of the underlying biology of the disease. In 1996 we disco vered that myeloma cells express both the cytokine Hepatocyte Growth Factor (HGF) and its receptor c-Met. The presence of high levels of HGF in the sera or bone marrow plasma of myeloma patients predicts a poor prognosis. We have now obtained evidence tha t HGF may be important for both the growth of myeloma cells and for the bone disease associated with multiple myeloma. The main goal of this project is to improve treatment of multiple myeloma by a translational research approach to the disease. The pro ject involves basic studies on myeloma- and bone-cells, genetic studies on deletions and translocations involved in the pathogenesis of multiple myeloma, and animal studies with an inhibitor of the HGF-receptor tyrosine kinase will be performed with the a im of validating HGF-signaling as a target for the treatment of multiple myeloma.