title: Latest advances and current challenges in the treatment of multiple myeloma.
abstract: Effectively treating patients with multiple myeloma is challenging. The development of therapeutic regimens over the past decade that incorporate the proteasome inhibitor bortezomib and the immunomodulatory drugs thalidomide and lenalidomide has been the cornerstone of improving the outcome of patients with myeloma. Although these treatment regimens have improved patient survival, nearly all patients eventually relapse. Our improved understanding of the biology of the disease and the importance of the microenvironment has translated into ongoing work to help overcome the challenge of relapse. Several classes of agents including next-generation proteasome inhibitors, immunomodulatory agents, selective histone-deacetylase inhibitors, antibody and antitumor immunotherapy approaches are currently undergoing preclinical and clinical evaluation. This Review provides an update on the latest advances in the treatment of multiple myeloma. In particular, we focus on novel therapies including modulating protein homeostasis, kinases inhibitors, targeting accessory cells and cytokines, and immunomodulatory agents. A discussion of the challenges associated with these therapeutic approaches is also presented.
authors.affiliation: Division of Hematology and Oncology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA. amahindra@gmail.com
authors.forename: Anuj
authors.initials: A
authors.lastname: Mahindra
authors.forename: Jacob
authors.initials: J
authors.lastname: Laubach
authors.forename: Noopur
authors.initials: N
authors.lastname: Raje
authors.forename: Nikhil
authors.initials: N
authors.lastname: Munshi
authors.forename: Paul G
authors.initials: PG
authors.lastname: Richardson
authors.forename: Kenneth
authors.initials: K
authors.lastname: Anderson
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D000077269:Lenalidomide; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000628:therapy; D011379:Prognosis; D011480:Protease Inhibitors / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011719:Pyrazines / Q000627:therapeutic use; D013792:Thalidomide / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D007155:Immunologic Factors; D011480:Protease Inhibitors; D047428:Protein Kinase Inhibitors; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D000077269:Lenalidomide