This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Multiple Myeloma (MM) is an incurable malignancy with a median survival of approximately three years with standard therapy. It accounts for 10% of malignant hematologic neoplasm with an estimated 10,800 deaths per year. The high mortality and morbidity of the disease, coupled with recent increased understanding of the role of cytokines in the pathogenesis of MM, have stimulated investigations using novel treatments that offer the potential to improve patient outcome. SCIO-469, an orally active new chemical entity that inhibits p38a mitogen-activated protein kinase (MAPK), with demonstrated anti-inflammatory and disease-modifying properties currently in Phase II clinical development for rheumatoid arthritis, has shown the ability to influence the cytokines, IL-6, vascular endothelial growth factory (VEGF), TNFa, and IL-1B involved in the pathogenesis of MM. P38a MAPK mediates the production of proinflammatory cytokines and other factors, including prostaglandin (PGE)2 receptor activator of nuclear factor-kB ligand (RANKL), and IL-11, that affect the pathogenesis of MM.
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