Characterization and Targeting of Platelet-Derived Growth Factor Receptor alpha (PDGFRA) in Inflammatory Breast Cancer (IBC)

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.

Anisomycin inhibits angiogenesis in ovarian cancer by attenuating the molecular sponge effect of the lncRNA‑Meg3/miR‑421/PDGFRA axis

“…There have been many reports on the functions of lncRNA-Meg3, PDGFRA and miR-421 in tumours, suggesting that these three molecules have very important regulatory effects on tumour proliferation and invasion (35,37,(45)(46)(47)(48)(49)(50)(51)(52). However, there have been no reports discussing the three in combination.…”

Awareness and current knowledge of breast cancer

“…Inflammatory breast cancer is the form of swollen breasts (red and warm) with dimples and/or broad ridges due to cancer cells blocking lymph vessels or channels in the skin over the breast. Though inflammatory breast cancer is uncommon and is tremendously fast-growing [ 49 ]. Treatment involves vigilant synchronization of all multidisciplinary strategies, including radiation therapy, surgery, chemotherapy and imaging.…”

PNME – A gene-gene parallel network module extraction method

“…Also, malignant breast cancer cells express higher levels of LAMA4 relative to pre-malignant cells [37]. (c) FAS Fas cell surface death receptor (FAS) shows significant associations with an increasing risk of breast cancer [38]. It has been observed that the risk of breast cancer may be elevated among women with polymorphisms in the FAS gene [39]. (d) PDGFRA Platelet-Derived Growth Factor Receptor Alpha (PDGFRA) has been found as being uniquely expressed and active in inflammatory breast cancer (IBC) patient tumor cells and may be a promising target for therapy in IBC [40]. PDGFRA activation signature is also associated with small metastasis-free survival. (e) BIRC3 BIRC3 is involved in chemo-resistance to doxorubicin in breast cancer cells [41].…”

“…Platelet-Derived Growth Factor Receptor Alpha (PDGFRA) has been found as being uniquely expressed and active in inflammatory breast cancer (IBC) patient tumor cells and may be a promising target for therapy in IBC [40]. PDGFRA activation signature is also associated with small metastasis-free survival.…”