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

Giulia Bresciani1, Angeliki Ditsiou2, Chiara Cilibrasi2

  • 1Section of Endocrinology and Internal Medicine, Department of Medical Sciences, University of Ferrara, Ferrara, Italy.

Endocrine Connections
|April 30, 2019
PubMed

Insights

Targeting epidermal growth factor receptor (EGFR) and insulin-like growth factor 1 receptor (IGF1R) shows promise for treating broncho-pulmonary neuroendocrine neoplasms (BP-NENs). These targeted therapies offer a more effective approach than current treatments for BP-NENs.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Broncho-pulmonary neuroendocrine neoplasms (BP-NENs) lack effective targeted therapies.
  • Sunitinib, a multi-receptor tyrosine kinase (RTK) inhibitor, shows efficacy in other neuroendocrine neoplasms (NENs) but its role in BP-NENs is unestablished.

Purpose of the Study:

  • To investigate the effects of RTK inhibition by sunitinib in BP-NENs.
  • To identify potential molecular targets for BP-NENs treatment by examining the roles of EGFR and IGF1R.

Main Methods:

  • Evaluated cell viability and caspase activation in BP-NEN cell lines and primary cultures.
  • Utilized AlphaScreen technology to measure phosphorylated EGFR and IGF1R levels.
  • Assessed the effects of sunitinib, erlotinib (EGFR inhibitor), and linsitinib (IGF1R inhibitor).

Main Results:

  • Sunitinib's antiproliferative effect was counteracted by EGF and IGF1, but not VEGF.
  • Sunitinib treatment decreased p-IGF1R, while co-treatment with IGF1 increased it.
  • Erlotinib and linsitinib demonstrated a stronger antiproliferative effect than sunitinib in BP-NEN cell lines.

Conclusions:

  • EGFR and IGF1R signaling pathways play a role in modulating sunitinib's efficacy in BP-NENs.
  • Targeting IGF1R and EGFR with specific inhibitors like linsitinib and erlotinib shows significant antiproliferative potential for BP-NENs treatment.
Keywords:
BP-NENsEGFRIGF1Rerlotiniblinsitinibsunitinib

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