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Updated: Aug 13, 2026

Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
Additive antitumor effects of gefitinib and imatinib on anaplastic thyroid cancer cells
Junichi Kurebayashi1, Sumiko Okubo, Yutaka Yamamoto
1Department of Breast and Thyroid Surgery, Kawasaki Medical School, Kurashiki, 701-0192, Okayama, Japan. kure@med.kawasaki-m.ac.jp
Purpose:
Anaplastic thyroid cancer (ATC) is one of the most aggressive malignancies. Although multidisciplinary treatments have been introduced, patients with this disease rarely survive longer than 1 year. These findings prompted us to investigate the antitumor activity of molecular targeting agents in thyroid cancer cells.
Methods:
Two tyrosine kinase inhibitors, gefitinib and imatinib, were tested in a poorly differentiated thyroid cancer cell line, KTC-1, and two ATC cell lines, KTC-2 and KTC-3.
Results:
All cell lines expressed not only a target molecule of gefitinib, HER1, but also a cognate receptor, HER2. They also expressed target molecules of imatinib, c-ABL and platelet-derived growth factor receptors at various levels. Both agents had modest antitumor activity in these cell lines. Combined treatment with gefitinib and imatinib led to an additional antitumor effect. Each agent induced apoptosis and their combined treatment enhanced apoptosis associated with the down-regulation of antiapoptotic proteins, Bcl-2 and Bcl-xL. Moreover, their combined treatment additionally inhibited the growth of KTC-3 xenografts in nude mice.
Conclusions:
These are the first findings to suggest that both gefitinib and imatinib have antitumor activity against ATC cells and that their combined use has greater activity than either drug alone.
Insights
Molecular targeting agents gefitinib and imatinib show antitumor activity against anaplastic thyroid cancer (ATC) cells. Combined treatment demonstrated enhanced apoptosis and inhibited tumor growth, suggesting greater efficacy than monotherapy for this aggressive cancer.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Anaplastic thyroid cancer (ATC) is a highly aggressive malignancy with a poor prognosis, often with survival less than one year despite multidisciplinary treatments.
- Investigating novel therapeutic strategies, including molecular targeting agents, is crucial for improving outcomes in ATC patients.
Purpose of the Study:
- To evaluate the antitumor activity of two tyrosine kinase inhibitors, gefitinib and imatinib, in anaplastic thyroid cancer cell lines.
- To determine the efficacy of combined gefitinib and imatinib treatment against ATC cells and xenografts.
Main Methods:
- Tested gefitinib and imatinib on poorly differentiated thyroid cancer (KTC-1) and ATC cell lines (KTC-2, KTC-3).
- Assessed expression of target molecules (HER1, HER2, c-ABL, PDGF receptors) in cell lines.
- Evaluated antitumor activity, apoptosis induction, and effects on antiapoptotic proteins (Bcl-2, Bcl-xL).
- Investigated combined treatment efficacy in KTC-3 xenografts in nude mice.
Main Results:
- All tested cell lines expressed target molecules for both gefitinib and imatinib.
- Both gefitinib and imatinib exhibited modest antitumor activity individually.
- Combined treatment with gefitinib and imatinib showed an additive antitumor effect, enhanced apoptosis, and downregulated Bcl-2 and Bcl-xL.
- Combined therapy significantly inhibited KTC-3 xenograft growth in vivo.
Conclusions:
- Gefitinib and imatinib possess antitumor activity against anaplastic thyroid cancer cells.
- Combination therapy with gefitinib and imatinib demonstrates superior efficacy compared to monotherapy.
- These findings support the potential of combined tyrosine kinase inhibition as a therapeutic strategy for anaplastic thyroid cancer.
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