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Heske CM, Yeung C, Mendoza A, et al. The Role of PDGFR-β Activation in Acquired Resistance to IGF-1R Blockade in Preclinical Models of Rhabdomyosarcoma. Transl Oncol. 2016;9(6):540-547doi: 10.1016/j.tranon.2016.09.002.
Heske, C. M., Yeung, C., Mendoza, A., Baumgart, J. T., Edessa, L. D., Wan, X., & Helman, L. J. (2016). The Role of PDGFR-β Activation in Acquired Resistance to IGF-1R Blockade in Preclinical Models of Rhabdomyosarcoma. Translational oncology, 9(6), 540-547. https://doi.org/10.1016/j.tranon.2016.09.002
Heske, Christine M, et al. "The Role of PDGFR-β Activation in Acquired Resistance to IGF-1R Blockade in Preclinical Models of Rhabdomyosarcoma." Translational oncology vol. 9,6 (2016): 540-547. doi: https://doi.org/10.1016/j.tranon.2016.09.002
Heske CM, Yeung C, Mendoza A, Baumgart JT, Edessa LD, Wan X, Helman LJ. The Role of PDGFR-β Activation in Acquired Resistance to IGF-1R Blockade in Preclinical Models of Rhabdomyosarcoma. Transl Oncol. 2016 Dec;9(6):540-547. doi: 10.1016/j.tranon.2016.09.002. Epub 2016 Nov 16. PMID: 27835791; PMCID: PMC5114528.
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Transl Oncol. 2016 Dec;9(6):540-547. doi: 10.1016/j.tranon.2016.09.002. Epub 2016 Nov 16.

The Role of PDGFR-β Activation in Acquired Resistance to IGF-1R Blockade in Preclinical Models of Rhabdomyosarcoma.

Translational oncology

Christine M Heske, Choh Yeung, Arnulfo Mendoza, Joshua T Baumgart, Leah D Edessa, Xiaolin Wan, Lee J Helman

Affiliations

  1. Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: [email protected].
  2. Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

PMID: 27835791 PMCID: PMC5114528 DOI: 10.1016/j.tranon.2016.09.002

Abstract

To determine what alternative pathways may act as mechanisms of bypass resistance to type 1 insulin-like growth factor receptor (IGF-1R) blockade in rhabdomyosarcoma (RMS), we compared expression of receptor tyrosine kinase activity in a number of IGF-1R antibody-resistant and -sensitive RMS cell lines. We found that platelet-derived growth factor receptor β (PDGFR-β) activity was upregulated in three xenograft-derived IGF-1R antibody-resistant cell lines that arose from a highly sensitive fusion-positive RMS cell line (Rh41). Furthermore, we identified four additional fusion-negative RMS cell lines that similarly upregulated PDGFR-β activity when selected for IGF-1R antibody resistance in vitro. In the seven cell lines described, we observed enhanced growth inhibition when cells were treated with dual IGF-1R and PDGFR-β inhibition in vitro. In vivo studies have confirmed the enhanced effect of targeting IGF-1R and PDGFR-β in several mouse xenograft models of fusion-negative RMS. These findings suggest that PDGFR-β acts as a bypass resistance pathway to IGF-1R inhibition in a subset of RMS. Therapy co-targeting these receptors may be a promising new strategy in RMS care.

Published by Elsevier Inc.

References

  1. Cancer Discov. 2013 May;3(5):534-47 - PubMed
  2. Int J Cancer. 1998 Apr 13;76(2):223-7 - PubMed
  3. J Clin Oncol. 2011 Dec 1;29(34):4541-7 - PubMed
  4. Cancer Res. 2010 Sep 15;70(18):7221-31 - PubMed
  5. Clin Cancer Res. 2014 Feb 1;20(3):658-67 - PubMed
  6. Neoplasia. 2015 Apr;17(4):358-66 - PubMed
  7. Cancer Res. 2005 Nov 15;65(22):10123-7 - PubMed
  8. Cell Growth Differ. 1990 Jul;1(7):325-31 - PubMed
  9. Clin Cancer Res. 2012 Jul 15;18(14):3780-90 - PubMed
  10. Cancer Res. 2008 Aug 1;68(15):6260-70 - PubMed
  11. Cancer Res. 2003 Dec 15;63(24):8912-21 - PubMed
  12. J Cell Physiol. 2000 Apr;183(1):1-9 - PubMed
  13. Cancer Res. 2012 Nov 15;72 (22):5889-99 - PubMed
  14. Oncologist. 1999;4(1):34-44 - PubMed
  15. Mol Cancer Ther. 2011 Apr;10(4):697-707 - PubMed
  16. Cancer Res. 1998 Oct 1 ;58(19):4426-33 - PubMed
  17. Nat Clin Pract Oncol. 2007 Oct;4(10):591-602 - PubMed
  18. Cancer Res. 2009 Jan 1;69(1):161-70 - PubMed
  19. Cancer Res. 2008 Oct 1;68(19):8039-48 - PubMed
  20. Am J Pathol. 2009 Feb;174(2):550-64 - PubMed
  21. Cancer. 2014 Aug 15;120(16):2448-56 - PubMed
  22. Cancer Res. 2007 May 1;67(9):4408-17 - PubMed

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