FGFR genetic alterations predict for sensitivity to NVP-BGJ398, a selective pan-FGFR inhibitor
Menée sur des lignées cellulaires, cette étude identifie une amplification du gène FGFR1 en association avec la réponse à un composé appelé NVP-BGJ398, un inhibiteur sélectif de FGFR, pour le traitement de patients atteints d'un ostéosarcome
Patient stratification biomarkers that enable the translation of cancer genetic knowledge into clinical utility are essential for the successful and rapid development of emerging targeted anti-cancer therapeutics. Here we describe the identification of patient stratification biomarkers for NVP-BGJ398, a novel and selective FGFR inhibitor. By intersecting genome-wide gene expression and genomic alteration data with cell line sensitivity data across an annotated collection of cancer cell lines termed "Cancer Cell Line Encyclopedia", we show that genetic alterations for FGFR family members predict for sensitivity to NVP-BGJ398. For the first time, we report oncogenic FGFR1 amplification in osteosarcoma as a potential patient selection biomarker. Furthermore, we show that cancer cell lines harboring FGF19 copy number gain at the 11q13 amplicon are sensitive to NVP-BGJ398 only when concomitant expression of β-klotho occurs. Thus, our findings provide the rationale for the clinical development of FGFR inhibitors in selected cancer patients harboring tumors with the identified predictors of sensitivity
Cancer Discovery , résumé, 2012