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	Michael Ferguson, Pooja Hingorani, Abha A Gupta
Journal	American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting (Am Soc Clin Oncol Educ Book) Pg. 420-4 ( 2013) ISSN: 1548-8756 [Electronic] United States
PMID	23714564 (Publication Type: Journal Article, Review)
Chemical References	Antibodies, Monoclonal Hedgehog Proteins Neoplasm Proteins Protein Kinase Inhibitors Receptor Protein-Tyrosine Kinases Kinesins
Topics	Adolescent Antibodies, Monoclonal (administration & dosage) Antineoplastic Combined Chemotherapy Protocols (therapeutic use) Cell Cycle (drug effects) Cell Hypoxia (drug effects) Child Clinical Trials, Phase I as Topic Clinical Trials, Phase II as Topic Drug Screening Assays, Antitumor Hedgehog Proteins (antagonists & inhibitors) Humans Kinesins (antagonists & inhibitors) Molecular Targeted Therapy Multicenter Studies as Topic Neoplasm Proteins (antagonists & inhibitors) Prognosis Protein Kinase Inhibitors (administration & dosage) Receptor Protein-Tyrosine Kinases (antagonists & inhibitors) Rhabdomyosarcoma (drug therapy, epidemiology) Signal Transduction (drug effects)

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