title: Targeting receptor tyrosine kinases in osteosarcoma and Ewing sarcoma: current hurdles and future perspectives.
abstract: Osteosarcoma (OS) and Ewing sarcoma (ES) are the two most common types of primary bone cancer, which mainly affect children and young adults. Despite intensive multi-modal treatment, the survival of both OS and ES has not improved much during the last decades and new therapeutic options are awaited. One promising approach is the specific targeting of transmembrane receptor tyrosine kinases (RTKs) implicated in these types of bone cancer. However, despite encouraging in vitro and in vivo results, apart from intriguing results of Insulin-like Growth Factor-1 Receptor (IGF-1R) antibodies in ES, clinical studies are limited or disappointing. Primary resistance to RTK inhibitors is frequently observed in OS and ES patients, and even patients that initially respond well eventually develop acquired resistance. There are, however, a few remarks to make concerning the current set-up of clinical trials and about strategies to improve RTK-based treatments in OS and ES. This review provides an overview concerning current RTK-mediated therapies in OS and ES and discusses the problems observed in the clinic. More importantly, we describe several strategies to overcome resistance to RTK inhibitors which may significantly improve outcome of OS and ES patients.
authors.affiliation: Department of Medical Oncology, Radboud University Medical Centre, Nijmegen, The Netherlands. Electronic address: Emmy.Fleuren@radboudumc.nl.
authors.forename: Emmy D G
authors.initials: ED
authors.lastname: Fleuren
authors.affiliation: Department of Medical Oncology, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Yvonne M H
authors.initials: YM
authors.lastname: Versleijen-Jonkers
authors.affiliation: Department of Nuclear Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Otto C
authors.initials: OC
authors.lastname: Boerman
authors.affiliation: Department of Medical Oncology, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Winette T A
authors.initials: WT
authors.lastname: van der Graaf
mesh_terms: D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D006801:Humans; D058990:Molecular Targeted Therapy; D012516:Osteosarcoma / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000378:metabolism / Q000627:therapeutic use*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D017526:Receptor, IGF Type 1 / Q000276:immunology / Q000627:therapeutic use; D012512:Sarcoma, Ewing / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology
chemical_list: D047428:Protein Kinase Inhibitors; D020794:Receptor Protein-Tyrosine Kinases; D017526:Receptor, IGF Type 1
keywords: Bone cancer; Ewing sarcoma; Imaging; Osteosarcoma; Receptor tyrosine kinase