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Updated: May 16, 2026
Tumorsphere Derivation and Treatment from Primary Tumor Cells Isolated from Mouse Rhabdomyosarcomas
Published on: September 13, 2019
Systemic analysis of gene expression profiles identifies ErbB3 as a potential drug target in pediatric alveolar
Janne Nordberg1, John Patrick Mpindi, Kristiina Iljin
1Department of Medical Biochemistry and Genetics, University of Turku, Turku, Finland.
Abstract:
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.
Insights
Targeted therapies show promise for pediatric sarcomas like Ewing's sarcoma and rhabdomyosarcomas. Researchers identified specific gene targets, including ERBB3, EPHA2, and VEGF-C, offering new avenues for treatment.
Area of Science:
- Oncology
- Molecular Biology
- Systems Biology
Background:
- Pediatric sarcomas (rhabdomyosarcomas, Ewing's sarcoma, osteosarcoma) are aggressive with poor prognoses.
- Current therapies lack selectivity; targeted therapeutics are increasingly used in adults but understudied in children.
- Understanding gene expression in pediatric sarcomas is crucial for developing effective treatments.
Purpose of the Study:
- To analyze the expression of 24 clinically approved target genes in pediatric normal and malignant tissues.
- To identify potential therapeutic targets for pediatric sarcomas using a systems biology approach.
- To validate the role of identified targets in rhabdomyosarcoma development and growth.
Main Methods:
- Utilized the Genesapiens database for high-throughput analysis of human transcriptome data.
- Examined gene expression profiles in diverse pediatric normal and malignant tissues.
- Validated in silico findings through in vitro and in vivo experiments, including protein expression analysis and gene silencing studies.
Main Results:
- VEGF-C and EPHA2 were significantly upregulated in Ewing's sarcoma.
- ERBB3 was significantly upregulated in alveolar rhabdomyosarcomas.
- ErbB3 protein expression was confirmed in pediatric rhabdomyosarcoma; its overexpression promoted, while siRNA suppressed, tumor cell growth.
Conclusions:
- ERBB3, EPHA2, and VEGF-C are promising therapeutic targets for pediatric sarcomas.
- Targeted drugs against ErbB3, EphA2, or VEGF-C warrant further investigation for pediatric sarcoma treatment.
- This study highlights the potential of systems biology approaches in identifying novel pediatric cancer targets.
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