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EGF and IGF1 affect Sunitinib activity in BP-NEN: new putative targets beyond VEGFR?

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Version 2 2023-06-12, 09:05
Version 1 2023-06-09, 17:41
journal contribution
posted on 2023-06-12, 09:05 authored by Giulia Bresciani, Angeliki Ditsiou, Chiara Cilibrasi, Viviana Vella, Federico Rea, Marco Schiavon, Narciso Giorgio Cavallesco, Georgios GiamasGeorgios Giamas, Maria Chiara Zatelli, Teresa Gagliano
Broncho-Pulmonary Neuroendocrine Neoplasms (BP-NENs) are neoplasms orphan of an efficient therapy. Available medical treatments derived from clinical trials are not specific for the management of this malignancy. Sunitinib is a multi-receptor tyrosine-kinases (RTKs) inhibitor that has already shown its efficacy in NENs but there are not available data about its action in BP-NENs. Therefore, our aim was to understand the effects of RTKs inhibition promoted by Sunitinib in order to evaluate new putative targets useful in malignancy treatment. Since our results underlined a role for EGFR and IGF1R in modulating Sunitinib antiproliferative action, we investigated the effects of Erlotinib, an EGFR inhibitor, and Linsitinib, an IGF1R inhibitor, in order to understand their function in regulating cells behaviour. Cell viability and caspase activation were evaluated on two immortalized human BP-NEN cell lines and primary cultures. 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. Results showed a decrease of p-IGF1R after treatment with Sunitinib and an increase after co-treatment with IGF1. Then, 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. In conclusion, our results suggest that IGF1R and EGF1R could represent putative molecular targets in BP-NENs treatment.

History

Publication status

  • Published

File Version

  • Published version

Journal

Endocrine Connections

ISSN

2049-3614

Publisher

BioScientifica

Issue

6

Volume

8

Page range

680-690

Department affiliated with

  • Biochemistry Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2019-05-02

First Open Access (FOA) Date

2019-05-02

First Compliant Deposit (FCD) Date

2019-05-01

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