Cancer Stem Cells in Multiple Myeloma and the Development of Novel Therapeutic Strategies

Abstract Cancer stem cells (CSCs) in patients with multiple myeloma (MM) are a subpopulation of tumor cells characterized by self-renewal capacity, clonogenic growth, and remarkable drug resistance and are thus considered the principal cause of tumor relapse. Although the exact phenotype of these cells has not been established, several markers, including CD138 − , aldehyde dehydrogenase + , and side population cells, have been used to identify them. MM CSCs utilize common self-renewal pathways, such as Wingless, Hedgehog, Notch, and PI3K/Akt/mTOR, as well as bone marrow microenvironment-dependent pathways that can be targeted with novel drugs. Combination therapies with (1) agents that would target MM CSCs plus (2) conventional anti-MM drugs that affect the bulk of tumor plasma cells are expected to provide a promising strategy for the possible transformation of MM into a chronic disease and eventually for the cure of MM.