title: Less Can Be More for Gene Dose and Drug Sensitivity.
abstract: CDK4 is preclinically validated as a therapeutic target in PAX3-FOXO1 fusion gene-positive rhabdomyosarcomas. Pharmacologic targeting showed sensitivity but, contrary to expectation, CDK4 genomic amplification and overexpression associated with 25% of cases that exhibited the lowest sensitivities. This emphasizes the importance of tumor-specific preclinical studies to define and understand drug sensitivity.
authors.affiliation: Divisions of Molecular Pathology and Cancer Therapeutics, The Institute of Cancer Research, London, United Kingdom.
authors.forename: Susanne A
authors.initials: SA
authors.lastname: Gatz
authors.affiliation: Divisions of Molecular Pathology and Cancer Therapeutics, The Institute of Cancer Research, London, United Kingdom. janet.shipley@icr.ac.uk.
authors.forename: Janet M
authors.initials: JM
authors.lastname: Shipley
mesh_terms: D000818:Animals; D051358:Cyclin-Dependent Kinase 4 / Q000037:antagonists & inhibitors* / Q000235:genetics*; D051361:Cyclin-Dependent Kinase 6 / Q000037:antagonists & inhibitors*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D006801:Humans; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D012208:Rhabdomyosarcoma / Q000235:genetics*
chemical_list: D015514:Oncogene Proteins, Fusion; D047428:Protein Kinase Inhibitors; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6