Multiple Myeloma (MM) accounts for about 10% of hematologic malignancies and it is the second most frequent hematologic neoplasm after lymphomas. The exact etiology of MM is still unknown and, despite the introduction of more effective and safe drugs in recent years, MM still remains an incurable disease. Intrinsic and acquired resistance of malignant B cells to pharmacological treatments still represents an obstacle for survival improvement. Activation of the Hepatocyte Growth Factor/c-MET axis has been reported as involved in MM pathogenesis: Hepatocyte Growth Factor (HGF) levels are in fact higher in sera from MM patients than in healthy controls, the HGF/c-MET pathway may be activated in autocrine or paracrine manner, and it is interesting to note that a higher c-MET phosphorylation is associated with disease progression. A number of studies have further demonstrated the over-activation of c-MET either in resistant cell lines or in primary malignant plasma cells purified from Bone Marrow of patients resistant to chemotherapy. For this reason c-MET has been proposed as a potential marker of multidrug resistance in the disease. We have here first summarized the potential role of HGF/c-MET interaction in disease evolution and then described novel approaches targeting this axis which could be conceptually utilized, alone or in combination with standard therapies, to treat MM and possibly to overcome drug resistance.
The HGF/c-MET axis as a potential target to overcome survival signals and improve therapeutic efficacy in multiple myeloma
Paolo Giannoni;
2021-01-01
Abstract
Multiple Myeloma (MM) accounts for about 10% of hematologic malignancies and it is the second most frequent hematologic neoplasm after lymphomas. The exact etiology of MM is still unknown and, despite the introduction of more effective and safe drugs in recent years, MM still remains an incurable disease. Intrinsic and acquired resistance of malignant B cells to pharmacological treatments still represents an obstacle for survival improvement. Activation of the Hepatocyte Growth Factor/c-MET axis has been reported as involved in MM pathogenesis: Hepatocyte Growth Factor (HGF) levels are in fact higher in sera from MM patients than in healthy controls, the HGF/c-MET pathway may be activated in autocrine or paracrine manner, and it is interesting to note that a higher c-MET phosphorylation is associated with disease progression. A number of studies have further demonstrated the over-activation of c-MET either in resistant cell lines or in primary malignant plasma cells purified from Bone Marrow of patients resistant to chemotherapy. For this reason c-MET has been proposed as a potential marker of multidrug resistance in the disease. We have here first summarized the potential role of HGF/c-MET interaction in disease evolution and then described novel approaches targeting this axis which could be conceptually utilized, alone or in combination with standard therapies, to treat MM and possibly to overcome drug resistance.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.