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Pediatric sarcomas, including rhabdomyosarcomas, Ewing’s sarcoma, and osteosarcoma, are aggressive tumors with poor survival rates. To overcome problems associated with nonselectivity of the current therapeutic approaches, targeted therapeutics have been developed. Currently, an increasing number of such drugs are used for treating malignancies of adult patients but little is known about their effects in pediatric patients. We analyzed expression of 24 clinically approved target genes in a wide variety of pediatric normal and malignant tissues using a novel high-throughput systems biology approach. Analysis of the Genesapiens database of human transcriptomes demonstrated statistically significant up-regulation of  VEGFC  and  EPHA2  in Ewing’s sarcoma, and  ERBB3  in alveolar rhabdomyosarcomas.  In silico  data for  ERBB3  was validated by demonstrating ErbB3 protein expression in pediatric rhabdomyosarcoma  in vitro  and  in vivo .  ERBB3  overexpression promoted whereas  ERBB3 -targeted siRNA suppressed rhabdomyosarcoma cell gowth, indicating a functional role for ErbB3 signaling in rhabdomyosarcoma. These data suggest that drugs targeting ErbB3, EphA2 or VEGF-C could be further tested as therapeutic targets for pediatric sarcomas.

Systemic Analysis of Gene Expression Profiles Identifies ErbB3 as a Potential Drug Target in Pediatric Alveolar Rhabdomyosarcoma