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.