"Multiple Myeloma (MM) is a progressive and debilitating B-cell disorder typified by the accumulation and dissemination of malignant plasma cells in the bone marrow which subsequently induce osteolytic lesions. Despite recent advancement of new therapies for MM, patients ultimately develop drug resistance and succumb to the disease. This highlights the need to increase our understanding of the disease and to identify new myeloma targets for drug development. The growth and progression of myeloma is multifaceted and signaling through several cytokine/receptor pathways have been shown to be vital for the pathobiology of this disease. Evidence for the MET receptor signaling pathway being an important contributor to the pathogenesis of this disease has been mounting. Both MET and its ligand, hepatocyte growth factor (HGF), are expressed in an autocrine loop in most myeloma cell lines and primary patient samples, as discerned at both the mRNA and protein level.
Peclinical studies show strong indication for targeting MET in myeloma for both reducing tumor burden in MET- dependent tumors and for alleviating bone disease. The clinical trial with tivantinib shows promise of MET being a viable therapeutic target. Future clinical trials need to be planned where myeloma patient populations are selected which have high serum HGF levels or possibly high plasma-cell MET levels for targeting this pathway. Additionally, monitoring of bone disease may also prove advantageous for e valuating the treatment benefit. The use of these criteria will allow for a more applicable means to effectively assess MET inhibitors as a therapeutic strategy in myeloma.
Last date updated on July, 2014