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An Orthotopic Mouse Model of Anaplastic Thyroid Carcinoma
07:01

An Orthotopic Mouse Model of Anaplastic Thyroid Carcinoma

Published on: April 17, 2013

Epidermal growth factor receptor as a therapeutic target in human thyroid carcinoma: mutational and functional

Constantine S Mitsiades1, Vassiliki Kotoula, Vassiliki Poulaki

  • 1Department of Medical Oncology, Dana-Farber Cancer Institute, Mayer Building, Room M555, 44 Binney Street, Boston, Massachusetts 02115, USA. Constantine_Mitsiades@dfci.harvard.edu

The Journal of Clinical Endocrinology and Metabolism
|July 11, 2006
PubMed
Abstract

Insights

Thyroid cancer cells show poor response to EGFR inhibitors like AEE788. While rare EGFR mutations may benefit some patients, more research is needed to confirm efficacy of these targeted therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Epidermal growth factor receptor (EGFR) is a key signaling molecule in normal and cancerous tissues.
  • EGFR inhibitors show efficacy in non-small-cell lung cancer with specific EGFR mutations.
  • The EGFR pathway is implicated in the development of thyroid carcinoma.

Purpose of the Study:

  • To investigate EGFR expression, mutation status, and functional role in thyroid carcinoma.
  • To evaluate the in vitro sensitivity of thyroid carcinoma cell lines to AEE788, a dual EGFR/ErbB2 and VEGFR tyrosine kinase inhibitor.
  • To assess EGFR's mutational status, mRNA and protein expression, and phosphorylation in thyroid carcinoma specimens.

Main Methods:

  • Analysis of EGFR expression and mutation in 14 thyroid carcinoma cell lines and 62 thyroid carcinoma specimens.
  • In vitro sensitivity testing of cell lines to AEE788.
  • Evaluation of EGFR mRNA, protein expression, and phosphorylation status.

Main Results:

  • EGFR expression and phosphorylation were observed in thyroid carcinoma but not higher than in noncancerous thyroid tissue.
  • EGFR tyrosine kinase domain mutations were found in 3.2% of histological specimens, but not in cell lines.
  • Thyroid carcinoma cell lines exhibited significantly lower sensitivity to AEE788 compared to EGFR-mutant lung carcinoma cells.

Conclusions:

  • Thyroid carcinoma cells demonstrate limited responsiveness to AEE788 at clinically relevant concentrations in vitro.
  • EGFR-activating tyrosine kinase domain mutations may identify a small subset of thyroid cancer patients who could potentially benefit from EGFR inhibitors.
  • Further preclinical studies are necessary to establish the efficacy of EGFR inhibitors in thyroid cancer.

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