title: Drugs in early clinical development for the treatment of osteosarcoma.
abstract: Osteosarcomas are the main malignant primary bone tumours found in children and young adults. Conventional treatment is based on diagnosis and resection surgery, combined with polychemotherapy. This is a protocol that was established in the 1970s. Unfortunately, this therapeutic approach has reached a plateau of efficacy and the patient survival rate has not improved in the last four decades. New therapeutic approaches are thus required to improve the prognosis for osteosarcoma patients. Areas covered: From the databases available and published scientific literature, the present review gives an overview of the drugs currently in early clinical development for the treatment of osteosarcoma. For each drug, a short description is given of the relevant scientific data supporting its development. Expert opinion: Multidrug targeted approaches are set to emerge, given the heterogeneity of osteosarcoma subtypes and the multitude of therapeutic responses. The key role played by the microenvironment in the disease increases the number of therapeutic targets (such as macrophages or osteoclasts), as well as the master proteins that control cell proliferation or cell death. Ongoing phase I/II trials are important steps, not only for identifying new therapies with greater safety and efficacy, but also for better defining the role played by the microenvironment in the pathogenesis of osteosarcoma.
authors.affiliation: a Department of Oncology and Metabolism, Medical School , University of Sheffield , Sheffield , UK.|b INSERM, UMR 957, Pathophysiology of Bone Resorption and Therapy of Primary Bone Tumours, Equipe Ligue 2012, Faculty of Medicine , University of Nantes , Nantes , France.|c Nantes University Hospital , Nantes , France.|d European Associated Laboratory, Sarcoma Research Unit, Medical School , INSERM-University of Sheffield , Sheffield , UK.
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Heymann
authors.affiliation: a Department of Oncology and Metabolism, Medical School , University of Sheffield , Sheffield , UK.|d European Associated Laboratory, Sarcoma Research Unit, Medical School , INSERM-University of Sheffield , Sheffield , UK.
authors.forename: Hannah K
authors.initials: HK
authors.lastname: Brown
authors.affiliation: a Department of Oncology and Metabolism, Medical School , University of Sheffield , Sheffield , UK.|b INSERM, UMR 957, Pathophysiology of Bone Resorption and Therapy of Primary Bone Tumours, Equipe Ligue 2012, Faculty of Medicine , University of Nantes , Nantes , France.|c Nantes University Hospital , Nantes , France.|d European Associated Laboratory, Sarcoma Research Unit, Medical School , INSERM-University of Sheffield , Sheffield , UK.
authors.forename: Dominique
authors.initials: D
authors.lastname: Heymann
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002648:Child; D015195:Drug Design; D006801:Humans; D058990:Molecular Targeted Therapy; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology; D011379:Prognosis; D059016:Tumor Microenvironment; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents
keywords: Clinical trials; cancer-initiating cells; immunomodulation; immunotherapy; macrophages; microenvironment; osteosarcoma