Advances in the biology of multiple myeloma: therapeutic applications.
Recent advances in the biology of multiple myeloma cell growth and survival have suggested new avenues for treatment and potential cure of this disease. Adhesion molecules on the myeloma cell surface mediate their localization in the bone marrow via binding to extracellular matrix proteins and stromal cells. Stromal cell to tumor cell contact and the secretion of transforming growth factor by tumor cells triggers interleukin-6 secretion from stromal cells and paracrine tumor cell growth. CD40 activation of myeloma cells changes their cell surface phenotype, triggers autocrine interleukin-6 secretion, and can regulate myeloma cell cycle in a p53-dependent fashion. Interleukin-6 is both a growth and survival factor for myeloma cells, and delineation of the signaling cascades mediating its effects permits the development of novel therapies either to interrupt growth or trigger apoptosis. New immune therapies offer the opportunity to treat minimal residual disease after stem cell transplantation, thereby improving outcome. Selected donor lymphocyte infusions after allografting and infusion of activated autologous T cells following autografting are examples of adoptive immunotherapy. Myeloma cell to dendritic cell fusions have been used in a vaccination strategy both to prevent and treat myeloma in an animal model, providing the rationale for similar clinical trials in humans. For the first time, a variety of novel treatment strategies derived from advances in understanding the disease pathogenesis offer the potential to achieve long-term disease-free survival in patients with multiple myeloma.
Anderson
K
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Department of Medicine, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
D001854:Bone Marrow Cells; D002453:Cell Cycle; D005109:Extracellular Matrix; D018380:Hematopoietic Stem Cell Transplantation; D006566:Herpesviridae Infections; D019288:Herpesvirus 8, Human; D006801:Humans; D016219:Immunotherapy, Adoptive; D015850:Interleukin-6; D009101:Multiple Myeloma / Q000276:immunology / Q000473:pathology / Q000628:therapy / Q000821:virology; D011956:Receptors, Cell Surface; D015398:Signal Transduction
D015850:Interleukin-6; D011956:Receptors, Cell Surface