title: Emerging molecular-targeted therapies in early-phase clinical trials and preclinical models.
abstract: Within the context of modern cooperative group trials, modification of standard cytotoxic chemotherapy has not improved survival in patients with rhabdomyosarcoma (RMS) over the last 30 years. There is need and interest to incorporate novel targeted anticancer agents into the treatment plans for children and adolescents with newly diagnosed RMS; however, targets directly driven by FOXO1 translocation remain elusive, and molecular events driving translocation negative tumors similarly remain ill-defined. Thus, alternate pathways driving the tumors require identification and targeting. Herein, we describe targeted therapies that could be of interest in RMS, but whose inclusion in clinical trials is thus far limited by scientific and regulatory criteria. Sorafenib, pazopanib, crizotinib, TH-302, aurora-kinase inhibitors, and anaplastic lymphoma kinase (ALK)/c-MET inhibitors will be discussed. The current preclinical and clinical data available, as well as limitations and challenges for each, will be outlined.
authors.affiliation: From the Department of Hematology/Oncology, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN; Division of Hematology Oncology, Center for Cancer and Blood Disorders, Phoenix Children's Hospital, Phoenix, AZ; Division of Hematology/Oncology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Ferguson
authors.forename: Pooja
authors.initials: P
authors.lastname: Hingorani
authors.forename: Abha A
authors.initials: AA
authors.lastname: Gupta
mesh_terms: D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002453:Cell Cycle / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects; D002648:Child; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D004354:Drug Screening Assays, Antitumor; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D016547:Kinesins / Q000037:antagonists & inhibitors; D058990:Molecular Targeted Therapy; D015337:Multicenter Studies as Topic; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D012208:Rhabdomyosarcoma / Q000188:drug therapy* / Q000453:epidemiology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D053823:Hedgehog Proteins; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D020794:Receptor Protein-Tyrosine Kinases; D016547:Kinesins