PDGFR-A is a therapeutic target in alveolar rhabdomyosarcoma

E. Taniguchi, K. Nishijo, A. T. McCleish, J. E. Michalek, M. H. Grayson, A. J. Infante, H. E. Abboud, R. D. Legallo, S. J. Qualman, B. P. Rubin, C. Keller

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Alveolar rhabdomyosarcoma is an aggressive skeletal muscle cancer of childhood. Our initial studies of rhabdomyosarcoma gene expression for patients enrolled in a national clinical trial suggested that platelet-derived growth factor receptor A (PDGFR-A) may be a mediator of disease progression and metastasis. Using our conditional mouse tumor models that authentically recapitulate the primary mutations and metastatic progression of alveolar rhabdomyosarcomas in humans, we found by immunoblotting and immunokinase assays that PDGFR-A and its downstream effectors, mitogen-activated protein kinase and Akt, were highly activated in both primary and metastatic tumors. Inhibition of PDGFR-A by RNA interference, small molecule inhibitor or neutralizing antibody had a dramatic effect on tumor cell growth both in vitro and in vivo, although resistance evolved in one-third of tumors. These results establish proof-of-principal for PDGFR-A as a therapeutic target in alveolar rhabdomyosarcoma.

Original languageEnglish (US)
Pages (from-to)6550-6560
Number of pages11
JournalOncogene
Volume27
Issue number51
DOIs
StatePublished - Oct 30 2008
Externally publishedYes

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Alveolar Rhabdomyosarcoma
Platelet-Derived Growth Factor Receptors
Neoplasms
Muscle Neoplasms
Rhabdomyosarcoma
Therapeutics
RNA Interference
Mitogen-Activated Protein Kinases
Neutralizing Antibodies
Immunoblotting
Disease Progression
Skeletal Muscle
Clinical Trials
Neoplasm Metastasis
Gene Expression
Mutation
Growth

Keywords

  • Alveolar rhabdomyosarcoma
  • PDGFR-A
  • Therapeutic target

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Taniguchi, E., Nishijo, K., McCleish, A. T., Michalek, J. E., Grayson, M. H., Infante, A. J., ... Keller, C. (2008). PDGFR-A is a therapeutic target in alveolar rhabdomyosarcoma. Oncogene, 27(51), 6550-6560. https://doi.org/10.1038/onc.2008.255

PDGFR-A is a therapeutic target in alveolar rhabdomyosarcoma. / Taniguchi, E.; Nishijo, K.; McCleish, A. T.; Michalek, J. E.; Grayson, M. H.; Infante, A. J.; Abboud, H. E.; Legallo, R. D.; Qualman, S. J.; Rubin, B. P.; Keller, C.

In: Oncogene, Vol. 27, No. 51, 30.10.2008, p. 6550-6560.

Research output: Contribution to journalArticle

Taniguchi, E, Nishijo, K, McCleish, AT, Michalek, JE, Grayson, MH, Infante, AJ, Abboud, HE, Legallo, RD, Qualman, SJ, Rubin, BP & Keller, C 2008, 'PDGFR-A is a therapeutic target in alveolar rhabdomyosarcoma', Oncogene, vol. 27, no. 51, pp. 6550-6560. https://doi.org/10.1038/onc.2008.255
Taniguchi E, Nishijo K, McCleish AT, Michalek JE, Grayson MH, Infante AJ et al. PDGFR-A is a therapeutic target in alveolar rhabdomyosarcoma. Oncogene. 2008 Oct 30;27(51):6550-6560. https://doi.org/10.1038/onc.2008.255
Taniguchi, E. ; Nishijo, K. ; McCleish, A. T. ; Michalek, J. E. ; Grayson, M. H. ; Infante, A. J. ; Abboud, H. E. ; Legallo, R. D. ; Qualman, S. J. ; Rubin, B. P. ; Keller, C. / PDGFR-A is a therapeutic target in alveolar rhabdomyosarcoma. In: Oncogene. 2008 ; Vol. 27, No. 51. pp. 6550-6560.
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