@article{322561d653454bd9b13687291b13ed7d,
title = "PDGFR-A is a therapeutic target in alveolar rhabdomyosarcoma",
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.",
keywords = "Alveolar rhabdomyosarcoma, PDGFR-A, Therapeutic target",
author = "E. Taniguchi and K. Nishijo and McCleish, {A. T.} and Michalek, {J. E.} and Grayson, {M. H.} and Infante, {A. J.} and Abboud, {H. E.} and Legallo, {R. D.} and Qualman, {S. J.} and Rubin, {B. P.} and C. Keller",
note = "Funding Information: Human muscle and frozen tumor samples were provided by the Cooperative Human Tissue Network (CHTN, Columbus, OH, USA), which is funded by the National Cancer Institute. The tissue samples obtained under an institutional review board-approved protocol have been previously described (that is, Cohort no. 2; Blandford et al., 2006). Other investigators may have received specimens from the same subjects. Funding Information: We thank Dr Frederic G Barr (The University of Pennsylvania School of Medicine) for providing Pax3:Fkhr cDNA and Pax7:Fkhr cDNA, and Dr Guillermina Lozano (University of Texas M.D. Anderson Cancer Center) for providing p53 cDNA. This work was funded in part by grants from NIH RO1CA 133229, the University Research Council (UTHSCSA), the Sarcoma Foundation of America, and the Amschwand Sarcoma Cancer Foundation. Animal care costs for this study were in part defrayed by a Nati onal Cancer Insti tu te Cente r grant to the San Antonio Cancer Center (Grant number P30 CA54174), of which CK is a member. We thank Dr Sharon B Murphy for critical reading of this article, and Gary Chisholm for statistical support.",
year = "2008",
month = oct,
day = "30",
doi = "10.1038/onc.2008.255",
language = "English (US)",
volume = "27",
pages = "6550--6560",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "51",
}