Less Can Be More for Gene Dose and Drug Sensitivity

Clin Cancer Res. 2015 Nov 1;21(21):4750-2. doi: 10.1158/1078-0432.CCR-15-1153. Epub 2015 Jul 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Comment

MeSH terms

  • Animals
  • Cyclin-Dependent Kinase 4 / antagonists & inhibitors*
  • Cyclin-Dependent Kinase 4 / genetics*
  • Cyclin-Dependent Kinase 6 / antagonists & inhibitors*
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Gene Amplification*
  • Humans
  • Oncogene Proteins, Fusion / genetics*
  • Protein Kinase Inhibitors / pharmacology*
  • Rhabdomyosarcoma / genetics*

Substances

  • Oncogene Proteins, Fusion
  • Protein Kinase Inhibitors
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6