title: Future novel single agent and combination therapies.
abstract: Although multiple myeloma (MM) remains an incurable bone marrow cancer, survival rates have dramatically improved over the past decade, most notably in the younger patient population. An understanding of MM biology and improvement in stem-cell transplantation, better supportive care, and novel therapies with higher efficacy and lower toxicity are all responsible for this improvement. Despite these trends, improvements among older patients remain modest, underscoring the need for innovative approaches. The availability of a rich pipeline of novel agents undergoing early-phase clinical trials in MM is an exciting and active area of research. Current novel agents targeting tumor and stromal compartments can be conceptualized as those that target membrane-bound receptors (insulin-like growth factor-1, vascular endothelial growth factor, CD40, etc.), intracellular signaling kinases (Janus kinase/signal transducers and activators of transcription, phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin, mitogen-activated protein kinase pathways), cell cycle molecular machinery (cyclin-dependent kinases inhibitors), epigenetic abnormalities (DNA methyltransferase and histyone deacetylase), protein dynamics (heat-shock protein 90, ubiquitin-proteasome system), and tumor vasculature and microenvironment (angiogenesis, integrins). This review highlights some of these novel agents tested either alone or in combination for the treatment of MM.
authors.affiliation: Leebow Institute of Myeloma Therapeutics and Jerome Lipper Multiple Myeloma Disease Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Cirstea
authors.forename: Sonia
authors.initials: S
authors.lastname: Vallet
authors.forename: Noopur
authors.initials: N
authors.lastname: Raje
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D003907:Dexamethasone / Q000627:therapeutic use; D018450:Disease Progression; D006801:Humans; D008558:Melphalan / Q000627:therapeutic use; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000276:immunology / Q000628:therapy; D009842:Oligopeptides / Q000627:therapeutic use; D011239:Prednisolone / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011719:Pyrazines / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D001897:Boronic Acids; D009842:Oligopeptides; D011480:Protease Inhibitors; D047428:Protein Kinase Inhibitors; D011719:Pyrazines; D000069286:Bortezomib; C524865:carfilzomib; D003907:Dexamethasone; D011239:Prednisolone; D008558:Melphalan