Publication: Biologic effects of platelet-derived growth factor receptor a blockade in uterine cancer
Issued Date
2014-05-15
Resource Type
ISSN
15573265
10780432
10780432
Other identifier(s)
2-s2.0-84901020811
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Mahidol University
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SCOPUS
Bibliographic Citation
Clinical Cancer Research. Vol.20, No.10 (2014), 2740-2750
Suggested Citation
Ju Won Roh, Jie Huang, Wei Hu, Xiaoyun Yang, Nicholas B. Jennings, Vasudha Sehgal, Bo HwaSohn, Hee Dong Han, Sun Joo Lee, Duangmani Thanapprapasr, Justin Bottsford-Miller, Behrouz Zand, Heather J. Dalton, Rebecca A. Previs, Ashley N. Davis, Koji Matsuo, Ju Seog Lee, Prahlad Ram, Robert L. Coleman, Anil K. Sood Biologic effects of platelet-derived growth factor receptor a blockade in uterine cancer. Clinical Cancer Research. Vol.20, No.10 (2014), 2740-2750. doi:10.1158/1078-0432.CCR-13-2507 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/33264
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Title
Biologic effects of platelet-derived growth factor receptor a blockade in uterine cancer
Author(s)
Abstract
Purpose: Platelet-derived growth factor receptor a (PDGFRa) expression is frequently observed in many kinds of cancer and is a candidate for therapeutic targeting. This preclinical study evaluated the biologic significance of PDGFRa and PDGFRa blockade (using a fully humanized monoclonal antibody, 3G3) in uterine cancer. Experimental Design: Expression of PDGFRa was examined in uterine cancer clinical samples and cell lines, and biologic effects of PDGFRa inhibition were evaluated using in vitro (cell viability, apoptosis, and invasion) and in vivo (orthotopic) models of uterine cancer. Results: PDGFRa was highly expressed and activated in uterine cancer samples and cell lines. Treatment with 3G3 resulted in substantial inhibition of PDGFRa phosphorylation and of downstream signaling molecules AKT and mitogen-Activated protein kinase (MAPK). Cell viability and invasive potential of uterine cancer cells were also inhibited by 3G3 treatment. In orthotopic mouse models of uterine cancer, 3G3 monotherapy had significant antitumor effects in the PDGFRa-positive models (Hec-1A, Ishikawa, Spec-2) but not in the PDGFRa-negative model (OVCA432). Greater therapeutic effects were observed for 3G3 in combination with chemotherapy than for either drug alone in the PDGFRa-positive models. The antitumor effects of therapy were related to increased apoptosis and decreased proliferation and angiogenesis. Conclusions: These findings identify PDGFRa as an attractive target for therapeutic development in uterine cancer. Clin Cancer Res © 2014 American Association for Cancer Research.
