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A Model for Perineural Invasion in Head and Neck Squamous Cell Carcinoma
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Antitumor effect of insulin-like growth factor-1 receptor inhibition in head and neck squamous cell carcinoma

Christine E Lehman1, Ashraf A Khalil1,2, Mark J Axelrod1,3

  • 1Department of Otolaryngology-Head and Neck Surgery, University of Virginia Health System, Charlottesville, Virginia, U.S.A.

The Laryngoscope
|August 22, 2019
PubMed
Abstract

Insights

Higher insulin-like growth factor-1 receptor (IGF1R) expression correlates with poorer survival in oral cavity squamous cell carcinoma. Two IGF1R tyrosine kinase inhibitors (TKIs) showed anticancer effects in head and neck squamous cell carcinoma cell lines.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Insulin-like growth factor-1 receptor (IGF1R) signaling is implicated in therapeutic resistance in head and neck squamous cell carcinoma (HNSCC).
  • Small molecule tyrosine kinase inhibitors (TKIs) targeting IGF1R activity present a potential therapeutic strategy for HNSCC.

Purpose of the Study:

  • To investigate the association between IGF1R expression and survival in oral cavity (OC) cancer.
  • To evaluate the in vitro antitumor effects of two IGF1R-TKIs, OSI-906 and BMS-754807, on HNSCC cell lines.

Main Methods:

  • Survival analysis using clinical data and tissue microarrays for IGF1R expression.
  • In vitro assays including immunoblotting, proliferation, viability, clonogenic survival, flow cytometry, and reverse phase protein array (RPPA) to assess drug responses.

Main Results:

  • Increased IGF1R expression was linked to reduced 5-year survival in stage III/IV oral cavity squamous cell carcinoma (OCSCC) patients (P=0.029).
  • Both OSI-906 and BMS-754807 inhibited IGF1R and Akt phosphorylation and proliferation in HNSCC cells; BMS-754807 demonstrated greater potency.
  • Both TKIs reduced HNSCC cell viability, with OSI-906 achieving complete cell elimination at 10 μM. RPPA revealed broad pathway inhibition, including HER3, Src, paxillin, and ezrin phosphorylation.

Conclusions:

  • OSI-906 and BMS-754807 effectively inhibit IGF1R activity in HNSCC cell lines, reducing pro-survival signaling.
  • These IGF1R antagonists exhibit antiproliferative and proapoptotic effects, suggesting potential as adjuvant therapies for HNSCC.
Keywords:
Head and neck squamous cell carcinomainsulin-like growth factor-1 receptortargeted molecular therapytyrosine kinase inhibitor

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