Methods and molecular pharmacokinetic biomarkers for a wide variety of signaling pathways in the orotic carboxamide amide triazole response

摘要

The present invention provides methods, pharmacodynamic biomarker signatures for a wide variety of signaling pathways in a subject cell sample (eg, growth hair) that respond to orotate carboxamidotriazole (CTO). In clinical trials, CTO has shown responses in several cancers with various genomic mutations. The present invention provides a diagnostic and prognostic assay that tracks the CTO response, which response is associated with several transcriptional signatures associated with tumor inhibition (EGFR, MEK, HDAC, RAS, GFS, WNT, HSP90 or non-potential dependent) Show differential expression ranging from -100 fold to +25 fold in calcium signaling (including calcium signaling), while tumor suppressor signatures (eg P53 or EGR1) are induced in the growth phase hair assay.