title: Emerging pathways as individualized therapeutic target of multiple myeloma.
abstract: BACKGROUND
  Multiple myeloma (MM) is an incurable plasma cell malignancy, which causes significant morbidity due to organ damage and bone tissue destruction. In recent years, novel drugs have become available for MM therapy thanks to the growing knowledge of disease pathobiology.
  
  
  METHODS
  Intrinsic genetic lesions, as well as the bone marrow microenvironment, contribute to the activation of proliferation and survival pathways, impairment of cell death mechanisms and drug resistance. The phosphatidylinositol 3-kinase (PI3K) and the Ras/mitogen-activated protein kinase (MAPK) cascades are the signaling pathways mainly involved in the MM development. In the last decade, several molecules interfering with growth and survival promoting signaling have been developed.
  
  
  CONCLUSIONS
  Despite the availability of novel therapeutics, MM still evolves into a drug-resistant phase and most patients die of progressive disease. Therefore, there is an urgent need of novel therapeutic strategies. Among a plethora of new investigational agents, microRNA (miRNA) represents the basis for the design of novel therapeutic strategies which basically rely on miRNA inhibition or miRNA replacement approaches and take benefit respectively from the use of miRNA inhibitors or synthetic miRNAs as well as from lipid-based nanoparticles as carriers for in vivo delivery.
authors.affiliation: Second University of Naples, Department of Biochemistry, Biophysics and General Pathology, Via S.M. Costantinopoli, 16, 80138 Naples, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Misso
authors.forename: Silvia
authors.initials: S
authors.lastname: Zappavigna
authors.forename: Maria
authors.initials: M
authors.lastname: Castellano
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Rosa
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Di Martino
authors.forename: Pierosandro
authors.initials: P
authors.lastname: Tagliaferri
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Tassone
authors.forename: Michele
authors.initials: M
authors.lastname: Caraglia
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy*; D057285:Precision Medicine; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents