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Title
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Characterization and targeting of Platelet-Derived Growth Factor Receptor Alpha (PDGFRA) in Inflammatory Breast Cancer (IBC)
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Author
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Abstract
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| PURPOSE: Inflammatory breast cancer (IBC) is arguably the deadliest form of breast cancer due to its rapid onset and highly invasive nature. IBC carries 5-and 10-year disease-free survival rates of similar to 45% and <20%, respectively. Multiple studies demonstrate that in comparison with conventional breast cancer, IBC has a unique molecular identity. Here, we have identified platelet-derived growth factor receptor alpha (PDGFRA) as being uniquely expressed and active in IBC patient tumor cells. EXPERIMENTAL DESIGN: Here we focus on characterizing and targeting PDGFRA in IBC. Using gene expression, we analyzed IBC patient samples and compared them with non-IBC patient samples. Further, using IBC cells in culture, we determined the effect of small molecules inhibitors in both in vitro and in vivo assays. RESULTS: In IBC patients, we show more frequent PDGFRA activation signature than non-IBC samples. In addition, the PDGFRA activation signature is associated with shorter metastasis-free survival in both uni- and multivariate analyses. We also demonstrate that IBC cells express active PDGFRA. Finally, we show that PDGFRA targeting by crenolanib (CP-868-596), but not imatinib (STI571), two small molecule inhibitors, interferes with IBC cell growth and emboli formation in vitro and tumor growth in vivo. CONCLUSIONS: Our data suggest that PDGFRA may be a promising target for therapy in IBC. |
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Language
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English
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Source (journal)
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Neoplasia
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Publication
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2017
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ISSN
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14765586
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DOI
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10.1016/J.NEO.2017.03.002
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Volume/pages
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19
:7
(2017)
, p. 564-573
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ISI
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000405460400005
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Pubmed ID
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28609680
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Full text (Publisher's DOI)
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Full text (open access)
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