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Vandetanib inhibits cell growth in EGFR-expressing cutaneous squamous cell carcinoma

Shinya Kitamura1, Takuya Maeda1, Teruki Yanagi1

  • 1Department of Dermatology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N15 W7, Kita-ku, Sapporo, 060-8638, Japan.

Biochemical and Biophysical Research Communications
|August 18, 2020
PubMed

Insights

Vandetanib effectively inhibits cutaneous squamous cell carcinoma (SCC) growth by targeting the epidermal growth factor receptor (EGFR). This study identifies vandetanib as a promising new treatment for advanced SCC, particularly in EGFR-expressing tumors.

Area of Science:

  • Oncology
  • Dermatology
  • Pharmacology

Background:

  • Advanced cutaneous squamous cell carcinoma (SCC) exhibits poor response to chemotherapy, causing significant morbidity and mortality.
  • Epidermal Growth Factor Receptor (EGFR) overexpression is common in advanced cutaneous SCC.
  • Vandetanib, a multi-tyrosine kinase inhibitor, targets EGFR, VEGFR2, and RET, and has shown efficacy in head and neck SCC.

Purpose of the Study:

  • To evaluate the efficacy of vandetanib against cutaneous SCC in vitro and in vivo.
  • To investigate the mechanism of action of vandetanib in cutaneous SCC.
  • To explore the clinical relevance of EGFR expression in cutaneous SCC.

Main Methods:

  • In vitro studies included cell viability, clonogenic assays, and cell death analysis using cutaneous SCC cells, normal human keratinocytes, and fibroblasts.
  • In vivo studies utilized xenograft tumor models with A431 SCC cells.
  • Mechanistic studies assessed EGFR phosphorylation, and clinical analysis examined EGFR expression in patient specimens.

Main Results:

  • Vandetanib inhibited proliferation and induced cell death in cutaneous SCC cells, but not in normal cells.
  • Vandetanib demonstrated anti-tumor effects in vivo xenograft models.
  • Vandetanib suppressed EGFR phosphorylation in SCC cells, and elevated EGFR expression was observed in clinical SCC specimens.

Conclusions:

  • Vandetanib is a potential therapeutic agent for cutaneous SCC.
  • The efficacy of vandetanib is linked to EGFR expression levels.
  • Vandetanib represents a novel treatment option for advanced cutaneous SCC, especially those with high EGFR expression.
Keywords:
Epidermal growth factor receptor (EGFR)KeratinocyteRearranged during transfection (RET)Squamous cell carcinoma (SCC)Vandetanib

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