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Endocrine Abstracts (2019) 63 P464 | DOI: 10.1530/endoabs.63.P464

1University of Ferrara, East Sussex, Italy; 2University of Sussex, Brighton, United Kingdom; 3University of Padua, Padua, Italy; 4University of Ferrara, Ferrara, Italy.

Background: Available medical treatments for Broncho-Pulmonary Neuroendocrine Neoplasm (BP-NENs) derived from clinical trials are not specific for the management of this malignancy. Sunitinib, a multi-receptor tyrosine-kinases (RTKs) inhibitor, mainly described as VEGFR inhibitor, has shown its efficacy in Pancreatic NENs but there are not available data about its action in BP-NENs. Our aim was to understand the effects of RTKs inhibition promoted by Sunitinib in order to evaluate new putative targets useful in malignancy treatment. Furthermore we investigated the effects of Erlotinib, an EGFR inhibitor, and Linsitinib, an IGF1R inhibitor, in order to understand their possible effects in BP-NENs.

Methods: BP-NENs cell lines and primary culture were treated with the indicated compound/growth factors. After treatment cell viability, apoptotic activation and RTK phosphorylation were evaluated.

Results: Our results showed that after treatment with Sunitinib and/or IGF1, EGF and VEGF, the antiproliferative effect of Sunitinib was counteracted by EGF and IGF1 but not by VEGF. Therefore, we evaluated with alpha-screen technology the phosphorylated EGFR and IGF1R levels in primary cultures treated with Sunitinib and/or EGF and IGF1 and found a decrease in p-IGF1R after treatment with Sunitinib and an increase after co-treatment with IGF1. We assessed cell viability and caspase activation on BP-NEN cell lines after treatment with Linsitinib and/or Erlotinib. Results demonstrate that these two agents have a stronger antiproliferative effect compared to Sunitinib.

Conclusion: Our results indicate that EGF and IGF1 impair Sunitinib activity on BP-NEN. IGF1R and EGF1R could represent putative molecular targets in BP-NENs treatment.

Volume 63

21st European Congress of Endocrinology

Lyon, France
18 May 2019 - 21 May 2019

European Society of Endocrinology 

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