NF-??B in the pathogenesis and treatment of multiple myeloma

PURPOSE OF REVIEW: This review aims to summarize recent advances in the mechanisms through which the activation of the transcription factor NF-kappaB contributes to the pathogenesis of multiple myeloma. RECENT FINDINGS: This transcription factor regulates expression of numerous genes involved in multiple myeloma pathogenesis, including growth, survival, immortalization, angiogenesis and metastasis. Recently, mutations of NF-kappaB signaling molecules have been identified in multiple myeloma cells. In addition, interactions between multiple myeloma cells and the bone marrow environment play critical roles in NF-kappaB activation as well as in multiple myeloma pathogenesis. Moreover, several drugs that are effective against multiple myeloma, including bortezomib, thalidomide, lenalidomide and arsenic trioxide, have been found to block activation of NF-kappaB. The combination of conventional chemotherapeutic drugs and those that block NF-kappaB activation has now proven to be effective in the treatment of multiple myeloma. SUMMARY: Recent studies further underscore the critical role of NF-kappaB in multiple myeloma pathogenesis and have provided the rationale for multiple myeloma therapy with NF-kappaB-specific inhibitors combined with conventional chemotherapeutic drugs.