title: Targeting signalling pathways for the treatment of multiple myeloma.
abstract: Multiple myeloma (MM) is characterised by the expansion of monoclonal immunoglobulin-secreting plasma cells. Despite recent advances in systemic and supportive therapy, it remains incurable, with a median survival of about three years. Development of MM is a multistep process associated with an increasing frequency of chromosomal abnormalities and complex translocations, which induce mutations in several proto-oncogenes and tumour suppressor genes. Furthermore, differentiation, maintenance, expansion and drug resistance of MM cells are dependent on multiple growth factors, cytokines, and chemokines, secreted by tumour cells, bone marrow stromal cells, and non-haematopoietic organs; as well as on direct tumour cell-stromal cell contact. Therefore, signalling pathways initiated by both mutated genes in MM cells as well as signals originating in the bone marrow microenvironment represent potential targets for intervention. Close collaboration between basic researchers and clinicians will be required to further improve our knowledge of MM pathophysiologically in order to translate advances from the bench to the bedside and improve patient outcome.
authors.affiliation: Department of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA. klaus_podar@dfci.harvard.edu
authors.forename: Klaus
authors.initials: K
authors.lastname: Podar
authors.forename: Teru
authors.initials: T
authors.lastname: Hideshima
authors.forename: Dharminder
authors.initials: D
authors.lastname: Chauhan
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology
chemical_list: D000970:Antineoplastic Agents