Moving disease biology from the laboratory to the clinic.
To address the urgent need for novel therapies for multiple myeloma (MM), long-term research efforts have characterized the mechanisms whereby MM cells home to the bone marrow and adhere to bone marrow stromal cells and extracellular matrix proteins. Research also characterizes the functional sequelae of this binding to identify targets for novel therapies. This article describes the mechanisms by which MM cells home to bone marrow and adhere to bone marrow stromal cells and extracellular matrix proteins, and describes the functional sequelae of this binding. Adhesion molecules that mediate MM cell binding to bone marrow stromal cells are identified, and the growth and survival advantage conferred by this binding is discussed. The biologic significance of cytokines in MM pathogenesis and the signaling cascades mediating their effects are delineated. Apoptotic and targeted therapeutic strategies to overcome drug resistance based on interrupting growth or triggering apoptotic-signaling cascades also are identified, providing the basis for novel biologically based therapies, such as thalidomide/immunomodulatory drugs and proteasome inhibitor PS-341.
Anderson
Kenneth C
KC
Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000502:physiology*; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000502:physiology*; D016228:Endothelial Growth Factors / Q000502:physiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D007372:Interferons / Q000502:physiology; D007694:Killer Cells, Natural / Q000502:physiology; D008222:Lymphokines / Q000502:physiology; D009101:Multiple Myeloma / Q000503:physiopathology* / Q000628:therapy*; D011480:Protease Inhibitors / Q000627:therapeutic use*; D011719:Pyrazines / Q000627:therapeutic use*; D015398:Signal Transduction; D033581:Stem Cell Transplantation; D013792:Thalidomide / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000970:Antineoplastic Agents; D001897:Boronic Acids; D015815:Cell Adhesion Molecules; D016207:Cytokines; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D011480:Protease Inhibitors; D011719:Pyrazines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D018799:Intercellular Adhesion Molecule-1; D013792:Thalidomide; D000069286:Bortezomib; D007372:Interferons