title: Signaling Pathways and Emerging Therapies in Multiple Myeloma.
abstract: Multiple myeloma (MM) is a devastating malignancy of antibody-producing plasma cells. In the absence of a single unifying genetic event contributing to disease manifestation, efforts have focused on understanding signaling events deregulated in myeloma plasma cells. MM cells are dependent on both cellular and non-cellular components of the tumor microenvironment such as bone marrow stromal cells, endothelial cells, and cytokines such as interleukin 6 (IL6), vascular endothelial growth factor (VEGF), and insulin-like growth factor (IGF) for their growth and survival. The cumulative effect of such interactions is the aberrant activation of numerous signal transduction pathways within the MM plasma cells leading to uncontrolled growth and prevention of apoptosis. Here, we will review our current understanding of some of the key signal transduction pathways dysregulated in MM and emerging therapies targeting these pathways in MM.
authors.affiliation: Division of Hematology, Mayo Clinic, 200, First Street SW, Rochester, MN, 55905, USA. Ramakrishnan.vijay@mayo.edu.
authors.forename: Vijay
authors.initials: V
authors.lastname: Ramakrishnan
authors.affiliation: Medical College of Wisconsin Milwaukee, Milwaukee, WI, 53226, USA. andsouza@mcw.edu.
authors.forename: Anita
authors.initials: A
authors.lastname: D'Souza
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
keywords: Akt; Multiple myeloma; NF-κB; Signaling; Signaling inhibitors; mTOR