RNA interference for multiple myeloma therapy: targeting signal transduction pathways

Jianfeng Guo, Sharon L McKenna, Michael E O’Dwyer, Mary R Cahill, Caitriona M O’Driscoll

Multiple myeloma (MM) is a hematological malignancy characterized by infiltration of malignant plasma cells in the bone marrow (BM) and end-organ damage to the bone, BM, kidney and immune system. Although current treatments have improved the treatment of MM, it still remains an incurable disease. RNA interference (RNAi) effectors such as microRNAs and small interference RNAs have shown potential to selectively downregulate genes implicated in the pathology of a range of diseases. Signaling pathways that facilitate growth, survival and migration of MM cells, provide resistance to conventional therapies, and therefore, target these signaling pathways will prove promising for MM treatment. Areas covered: This review focuses on signaling pathways associated with the development of myeloma cells and how interaction of these cells with the tumor microenvironment impacts disease progression. Together these elements provide potential therapeutic targets for RNAi in the future. Expert opinion: Recent advances in oncogenomic studies have revealed the molecular pathogenesis of MM, thus providing new therapeutic targets for RNAi therapy. Pre-clinical evidence suggests that non-viral delivery technology offers the potential to translate this concept into the next generation of RNAi-based therapeutics for MM.