characterization and targeting of platelet-derived growth factor receptor alpha (pdgfra) in inflammatory breast cancer (ibc)

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ID: 221160
2017
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Abstract
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 ~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.
Reference Key
joglekar-javadekar2017neoplasia:characterization Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Madhura Joglekar-Javadekar;Steven Van Laere;Michael Bourne;Manal Moalwi;Pascal Finetti;Peter B. Vermeulen;Daniel Birnbaum;Luc Y. Dirix;Naoto Ueno;Monique Carter;Justin Rains;Abhijit Ramachandran;Francois Bertucci;Kenneth L. van Golen
Journal ACS chemical neuroscience
Year 2017
DOI
10.1016/j.neo.2017.03.002
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