Identification of sensitivity markers for BMS-536924, an inhibitor for insulin-like growth factor-1 receptor

3506 Background: Insulin-like growth factor-1 receptor (IGF-1R) signaling is an important regulator of mitogenesis, transformation to the oncogenic phenotype and anti-apoptotic effects in malignant cells. Over-expression of IGF-1R, seen in many tumors, may confer a growth advantage or drug resistance. A potent small-molecule inhibitor (BMS-536924) of IGF-1R tyrosine kinase showed anti-tumor activity in sarcoma, prostate, colon and pancreatic tumor models. One of the integral goals in the development of BMS-536924 as a cancer therapeutic is to identify molecular biomarkers predictive of response to the drug that ultimately will aid in selecting the patients who are most likely to benefit. Methods: The sensitivity (IC50) to BMS-536924 was determined for a panel of 29 pediatric sarcoma and neuroblastoma cell lines. Both microarray and LC/MS based protein profiling were utilized to analyze the baseline gene or protein expression level. Drug treatment studies were performed using two rhabdomyosarcoma cell line...