title: The insulin-like growth factor system in multiple myeloma: diagnostic and therapeutic potential.
abstract: Multiple myeloma (MM) is a highly heterogeneous plasma cell malignancy. The MM cells reside in the bone marrow (BM), where reciprocal interactions with the BM niche foster MM cell survival, proliferation, and drug resistance. As in most cancers, the insulin-like growth factor (IGF) system has been demonstrated to play a key role in the pathogenesis of MM. The IGF system consists of IGF ligands, IGF receptors, IGF binding proteins (IGFBPs), and IGFBP proteases and contributes not only to the survival, proliferation, and homing of MM cells, but also MM-associated angiogenesis and osteolysis. Furthermore, increased IGF-I receptor (IGF-IR) expression on MM cells correlates with a poor prognosis in MM patients. Despite the prominent role of the IGF system in MM, strategies targeting the IGF-IR using blocking antibodies or small molecule inhibitors have failed to translate into the clinic. However, increasing preclinical evidence indicates that IGF-I is also involved in the development of drug resistance against current standard-of-care agents against MM, including proteasome inhibitors, immunomodulatory agents, and corticoids. IGF-IR targeting has been able to overcome or revert this drug resistance in animal models, enhancing the efficacy of standard-of-care agents. This finding has generated renewed interest in the therapeutic potential of IGF-I targeting in MM. The present review provides an update of the impact of the different IGF system components in MM and discusses the diagnostic and therapeutic potentials.
authors.affiliation: Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel, Brussels, Belgium.|Department of Hematology, Aalborg Hospital, Aalborg University, Denmark.|Department of Biomedicin, Aarhus University, Aarhus, Denmark.
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Bieghs
authors.affiliation: Department of Hematology, Aalborg Hospital, Aalborg University, Denmark.|Clinical Cancer Research Center, Aalborg University Hospital, Denmark.|Department of Clinical Medicine, Aalborg University, Denmark.
authors.forename: Hans E
authors.initials: HE
authors.lastname: Johnsen
authors.affiliation: Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Ken
authors.initials: K
authors.lastname: Maes
authors.affiliation: Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Eline
authors.initials: E
authors.lastname: Menu
authors.affiliation: Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Els
authors.initials: E
authors.lastname: Van Valckenborgh
authors.affiliation: Department of Chemistry and Biotechnology, Aalborg University, Denmark.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Overgaard
authors.affiliation: Department of Biomedicin, Aarhus University, Aarhus, Denmark.
authors.forename: Mette
authors.initials: M
authors.lastname: Nyegaard
authors.affiliation: Division of Endocrinology, Metabolism and Nutrition, Endocrine Research Unit, Mayo Clinic, Rochester, NY, USA.
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Conover
authors.affiliation: Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Karin
authors.initials: K
authors.lastname: Vanderkerken
authors.affiliation: Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Elke
authors.initials: E
authors.lastname: De Bruyne
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D049109:Cell Proliferation; D002470:Cell Survival; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood / Q000378:metabolism*; D051379:Mice; D058990:Molecular Targeted Therapy / Q000379:methods; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000473:pathology; D009374:Neoplasms, Experimental / Q000097:blood / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism; D010014:Osteolysis / Q000378:metabolism; D010766:Phosphorylation; D011379:Prognosis; D011485:Protein Binding / Q000187:drug effects; D017451:Receptors, Somatomedin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013002:Somatomedins / Q000032:analysis / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D017451:Receptors, Somatomedin; D013002:Somatomedins; D010450:Endopeptidases
keywords: IGF-I targeting; multiple myeloma; insulin-like growth factor