title: Optimal management of Ewing sarcoma family of tumors: recent developments in systemic therapy.
abstract: The Ewing sarcoma family of tumors (ESFT) is defined by cell surface expression of CD99 and a translocation involving EWS and an ETS partner. Cytotoxic chemotherapy remains the benchmark of first- and second-line therapy, and although the majority of patients with localized disease are cured, almost one third of patients relapse or progress from their disease. Moreover, cure remains elusive in most patients who present with distant metastases. In recent years, the ESFT literature has been dominated by reports of attempts at modulating the insulin-like growth factor (IGF) receptor (IGFR). Unfortunately, three phase II studies examining inhibiting antibodies to IGFR-1 published disappointing results. Whether these results were due to failure to modulate the pathway or other limitations in study design and/or patient selection remain unclear. Other novel strategies currently being investigated in ESFT include tyrosine kinase, mammalian target of rapamycin (mTOR), and poly(ADP-ribose) polymerase (PARP) inhibitors.
authors.affiliation: The Division of Hematology/Oncology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON, M5G 1N6, Canada, cormacowens@yahoo.com.
authors.forename: Cormac
authors.initials: C
authors.lastname: Owens
authors.forename: Lesleigh S
authors.initials: LS
authors.lastname: Abbott
authors.forename: Abha A
authors.initials: AA
authors.lastname: Gupta
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D012512:Sarcoma, Ewing / Q000188:drug therapy* / Q000235:genetics / Q000601:surgery; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D014178:Translocation, Genetic
chemical_list: D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D047428:Protein Kinase Inhibitors; D007334:Insulin-Like Growth Factor I; C546842:MTOR protein, human; D011505:Protein-Tyrosine Kinases; D058570:TOR Serine-Threonine Kinases