Sarcoma gene expression and response to approved and investigational agents: Focus on osteosarcoma.

Abstract

e22067 Background: Sarcomas are rare heterogeneous cancers with significant unmet medical need. Identification of gene expression associated with response to potential novel clinical agents is important. Methods: Response of 62 adult and pediatric human sarcoma cell lines was evaluated against approved (93 drugs) and investigational (350 compounds) anticancer agents. Lines were exposed to 9 concentrations (10uM-1.5nM) for 96h (384-well format); cell viability was determined using Alamar Blue. Gene expression was generated using the Affymetrix Human Exon 1.0 ST arrays according to manufacturer’s instructions. Results: The RTK ErbB family had variable gene expression across the lines. High ERBB4 expression was evident in 50% of Ewing sarcoma lines, and was highly expressed in 2/10 osteosarcoma lines. Of 18 approved and investigational broad spectrum kinase inhibitors and selective FGFR, KIT and MET inhibitors, the most sensitive osteosarcoma lines included CHA59, HOS, and Hu09 while SA-OS-2 was less sensiti...