Targeting multiple myeloma cells and their bone marrow microenvironment.

Although multiple myeloma (MM) is sensitive to chemotherapy and radiation therapy, long-term disease-free survival is rare, and MM remains incurable despite conventional and high-dose therapies. Direct (cell-cell contact) and soluble (via cytokines) forms of interactions between MM cells and bone marrow stroma regulate growth, survival, and homing of MM cells. These interactions also play a critical role in angiogenesis and in myeloma bone disease. In recent years, several studies have established the biologic significance of cytokines in MM pathogenesis and delineated signaling cascades mediating their effects, providing the framework for related novel therapies targeting not only the MM cell, but also the bone marrow microenvironment.