title: Dissecting the multiple myeloma-bone microenvironment reveals new therapeutic opportunities.
abstract: Multiple myeloma is a plasma cell skeletal malignancy. While therapeutic agents such as bortezomib and lenalidomide have significantly improved overall survival, the disease is currently incurable with the emergence of drug resistance limiting the efficacy of chemotherapeutic strategies. Failure to cure the disease is in part due to the underlying genetic heterogeneity of the cancer. Myeloma progression is critically dependent on the surrounding microenvironment. Defining the interactions between myeloma cells and the more genetically stable hematopoietic and mesenchymal components of the bone microenvironment is critical for the development of new therapeutic targets. In this review, we discuss recent advances in our understanding of how microenvironmental elements contribute to myeloma progression and, therapeutically, how those elements can or are currently being targeted in a bid to eradicate the disease.
authors.affiliation: Tumor Biology Department, SRB-3, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Blvd, Tampa, FL, 33612, USA.
authors.forename: G
authors.initials: G
authors.lastname: Shay
authors.affiliation: Department of Pharmaceutical Sciences and The Alexander B. Osborn Hematopoietic Malignancy and Transplantation Program, West Virginia University, Morgantown, WV, 26506, USA.
authors.forename: L
authors.initials: L
authors.lastname: Hazlehurst
authors.affiliation: Tumor Biology Department, SRB-3, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Blvd, Tampa, FL, 33612, USA. conor.lynch@moffitt.org.
authors.forename: C C
authors.initials: CC
authors.lastname: Lynch
mesh_terms: D001853:Bone Marrow / Q000473:pathology; D001842:Bone and Bones / Q000166:cytology* / Q000473:pathology; D000069286:Bortezomib / Q000627:therapeutic use; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D006801:Humans; D000077269:Lenalidomide; D058990:Molecular Targeted Therapy / Q000379:methods*; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D009842:Oligopeptides / Q000627:therapeutic use; D061988:Proteasome Inhibitors / Q000627:therapeutic use; D013792:Thalidomide / Q000031:analogs & derivatives / Q000627:therapeutic use; D059016:Tumor Microenvironment / Q000502:physiology*
chemical_list: D009842:Oligopeptides; D061988:Proteasome Inhibitors; D013792:Thalidomide; D000069286:Bortezomib; C524865:carfilzomib; D000077269:Lenalidomide
keywords: Bone microenvironment; Multiple myeloma; Therapeutic opportunities