title: Engaging Cell Death Pathways for the Treatment of Rhabdomyosarcoma.
abstract: Rhabdomyosarcoma (RMS), a malignant neoplasm of presumed mesenchymal origin, is the most common soft tissue cancer of childhood. Despite aggressive treatment, resistance to current therapies remains a challenge. The success of most cytotoxic chemotherapies requires intact programmed cell death (apoptosis) pathways. Defects in the cellular apoptotic program play a key role in the pathogenesis of RMS and contribute to chemotherapeutic resistance to current treatments. Targeting and engaging apoptotic pathways using small-molecule IAP antagonists, death-inducing ligands, reestablishing pannexin channel expression and activity, immunotherapies, or a combination of these approaches is expected to improve outcomes in RMS patients. There is a clear need to better understand the molecular basis of apoptotic resistance in RMS, which may provide an opportunity to identify the patients most likely to benefit from targeted treatments, and for the discovery of novel therapies.
authors.affiliation: Molecular Biomedicine Program, Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Christine C
authors.initials: CC
authors.lastname: Dobson
authors.affiliation: Molecular Biomedicine Program, Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada; Department of Surgery, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Langlois
authors.affiliation: Department of Pathology and Laboratory Medicine, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Grynspan
authors.affiliation: Molecular Biomedicine Program, Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada; Department of Surgery, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Kyle N
authors.initials: KN
authors.lastname: Cowan
authors.affiliation: Molecular Biomedicine Program, Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada; Department of Pediatrics, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Holcik
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D019008:Drug Resistance, Neoplasm; D006801:Humans; D012208:Rhabdomyosarcoma / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D000970:Antineoplastic Agents