title: Therapeutic targeting of hypoxia and hypoxia-inducible factor 1 alpha in multiple myeloma.
abstract: Multiple myeloma (MM) is a clonal B-cell malignancy characterized by accumulation of malignant plasma cells (PCs) within the bone marrow (BM). The PCs are in close contact with stromal cells, which secrete growth factors and cytokines, promoting tumor cell growth and survival. Despite the availability of new drugs with immunomodulatory properties targeting the neoplastic clone and its microenvironment, MM is still an incurable disease, with patients experiencing subsequent phases of remission and relapse, eventually leading to disease resistance and patient death. It is now well established that the MM BM microenvironment is hypoxic, a condition required for the activation of the hypoxia-inducible factor 1 alpha (HIF-1α). It has been shown that HIF-1α is constitutively expressed in MM even in normoxic conditions, suggesting that HIF-1α suppression might be part of a therapeutic strategy. Constitutively activated HIF-1α enhances neovascularization, increases glucose metabolism, and induces the expression of antiapoptotic proteins. HIF-1α is thought to be one of the most important molecular targets in the treatment of cancer, and a variety of chemical inhibitors for HIF-1α have been developed to date. This review examines the role of HIF-1α in MM and recent developments in harnessing the therapeutic potential of HIF-1α inhibition in MM.
authors.affiliation: Department of Experimental Diagnostic and Specialty Medicine (DIMES), Institute of Hematology, "L. & A. Seràgnoli," Bologna University, S. Orsola's University Hospital, Bologna, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Borsi
authors.affiliation: Department of Experimental Diagnostic and Specialty Medicine (DIMES), Institute of Hematology, "L. & A. Seràgnoli," Bologna University, S. Orsola's University Hospital, Bologna, Italy.
authors.forename: Carolina
authors.initials: C
authors.lastname: Terragna
authors.affiliation: Department of Experimental Diagnostic and Specialty Medicine (DIMES), Institute of Hematology, "L. & A. Seràgnoli," Bologna University, S. Orsola's University Hospital, Bologna, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Brioli
authors.affiliation: Department of Experimental Diagnostic and Specialty Medicine (DIMES), Institute of Hematology, "L. & A. Seràgnoli," Bologna University, S. Orsola's University Hospital, Bologna, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Tacchetti
authors.affiliation: Department of Experimental Diagnostic and Specialty Medicine (DIMES), Institute of Hematology, "L. & A. Seràgnoli," Bologna University, S. Orsola's University Hospital, Bologna, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Martello
authors.affiliation: Department of Experimental Diagnostic and Specialty Medicine (DIMES), Institute of Hematology, "L. & A. Seràgnoli," Bologna University, S. Orsola's University Hospital, Bologna, Italy. Electronic address: michele.cavo@unibo.it.
authors.forename: Michele
authors.initials: M
authors.lastname: Cavo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D015687:Cell Hypoxia; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000187:drug effects*; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit