title: RNA interference for multiple myeloma therapy: targeting signal transduction pathways.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: a 1 University College Cork, School of Pharmacy, Pharmacodelivery Group , Cork, Ireland.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Guo
authors.affiliation: b 2 University College Cork, Cork Cancer Research Centre , Cork, Ireland.
authors.forename: Sharon L
authors.initials: SL
authors.lastname: McKenna
authors.affiliation: c 3 Glycoscience Research Group, National University of Ireland , Galway, Ireland.|d 4 Department of Hematology National University of Ireland , Galway, Ireland.|e 5 Galway University Hospital , Galway, Ireland.
authors.forename: Michael E
authors.initials: ME
authors.lastname: O'Dwyer
authors.affiliation: f 6 Department of Haematology, Cork University Hospital , Cork, Ireland.
authors.forename: Mary R
authors.initials: MR
authors.lastname: Cahill
authors.affiliation: g 7 University College Cork, School of Pharmacy, Pharmacodelivery Group , Cork, Ireland +353 21 4901396 ; +353 21 4901656 ; caitriona.odriscoll@ucc.ie.
authors.forename: Caitriona M
authors.initials: CM
authors.lastname: O'Driscoll
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D018450:Disease Progression; D015536:Down-Regulation / Q000235:genetics; D006801:Humans; D009101:Multiple Myeloma / Q000235:genetics / Q000628:therapy*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D015398:Signal Transduction / Q000235:genetics; D059016:Tumor Microenvironment / Q000235:genetics
chemical_list: D034741:RNA, Small Interfering
keywords: RNAi-based therapy; myeloma signaling pathways; non-viral delivery vectors; the bone marrow microenvironment