title: Emerging strategies for targeting cell adhesion in multiple myeloma.
abstract: Multiple myeloma (MM) is an incurable hematological cancer involving proliferation of abnormal plasma cells that infiltrate the bone marrow (BM) and secrete monoclonal antibodies. The disease is clinically characterized by bone lesions, anemia, hypercalcemia, and renal failure. MM is presently treated with conventional therapies like melphalan, doxorubicin, and prednisone; or novel therapies like thalidomide, lenalidomide, and bortezomib; or with procedures like autologous stem cell transplantation. Unfortunately, these therapies fail to eliminate the minimal residual disease that remains persistent within the confines of the BM of MM patients. Mounting evidence indicates that components of the BM-including extracellular matrix, cytokines, chemokines, and growth factors-provide a sanctuary for subpopulations of MM. This co-dependent development of the disease in the context of the BM not only ensures the survival and growth of the plasma cells but contributes to de novo drug resistance. In addition, by fostering homing, angiogenesis, and osteolysis, this crosstalk plays a critical role in the progression of the disease. Not surprisingly then, over the past decade, several strategies have been developed to disrupt this communication between the plasma cells and the BM components including antibodies, peptides, and inhibitors of signaling pathways. Ultimately, the goal is to use these therapies in combination with the existing antimyeloma agents in order to further reduce or abolish minimal residual disease and improve patient outcomes.
authors.affiliation: Molecular Oncology Program, H Lee Moffitt Cancer Center, Tampa, FL, USA.
authors.forename: Rajesh R
authors.initials: RR
authors.lastname: Nair
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Gebhard
authors.forename: Michael F
authors.initials: MF
authors.lastname: Emmons
authors.forename: Lori A
authors.initials: LA
authors.lastname: Hazlehurst
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002448:Cell Adhesion / Q000187:drug effects; D018450:Disease Progression; D006801:Humans; D058990:Molecular Targeted Therapy; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents