Inhibition of Survivin with YM155 Induces Durable Tumor Response in Anaplastic Thyroid Cancer
Related Experiment Video
Updated: Apr 13, 2026
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
Amit Mehta1, Lisa Zhang2, Myriem Boufraqech2
1Endocrine Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland. Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.
Purpose:
Anaplastic thyroid cancer (ATC) is a rare but lethal malignancy without any effective therapy. The aim of this study is to use a high-throughput drug library screening to identify a novel therapeutic agent that targets dysregulated genes/pathways in ATC.
Experimentaldesign:
We performed quantitative high-throughput screening (qHTS) in ATC cell lines using a compound library of 3,282 drugs. Dysregulated genes in ATC were analyzed using genome-wide expression analysis and immunohistochemistry in human ATC tissue samples and ATC cell lines. In vitro and in vivo studies were performed for determining drug activity, effectiveness of targeting, and the mechanism of action.
Results:
qHTS identified 100 active compounds in three ATC cell lines. One of the most active agents was the first-in-class survivin inhibitor YM155. Genome-wide expression analysis and immunohistochemistry showed overexpression of survivin in human ATC tissue samples, and survivin was highly expressed in all ATC cell lines tested. YM155 significantly inhibited ATC cellular proliferation. Mechanistically, YM155 inhibited survivin expression in ATC cells. Furthermore, YM155 treatment reduced claspin expression, which was associated with S-phase arrest in ATC cells. In vivo, YM155 significantly inhibited growth and metastases and prolonged survival.
Conclusions:
Our data show that YM155 is a promising anticancer agent for ATC and that its target, survivin, is overexpressed in ATC. Our findings support the use of YM155 in clinical trials as a therapeutic option in advanced and metastatic ATC.
Insights
Anaplastic thyroid cancer (ATC) treatment shows promise with YM155, a survivin inhibitor. This drug effectively reduced tumor growth and metastasis in preclinical studies, offering hope for patients.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- Anaplastic thyroid cancer (ATC) is a rare, aggressive malignancy with limited therapeutic options.
- Identifying novel therapeutic targets and agents is crucial for improving patient outcomes in ATC.
Purpose of the Study:
- To identify a novel therapeutic agent for anaplastic thyroid cancer (ATC) through high-throughput drug screening.
- To investigate the efficacy and mechanism of action of identified agents in ATC.
Main Methods:
- Quantitative high-throughput screening (qHTS) of 3,282 compounds in ATC cell lines.
- Genome-wide expression analysis and immunohistochemistry to identify dysregulated genes in ATC.
- In vitro and in vivo studies to evaluate drug activity, targeting, and mechanism of action.
Main Results:
- qHTS identified 100 active compounds, with YM155 (surviving inhibitor) being highly effective.
- Survivin was found to be overexpressed in human ATC tissues and cell lines.
- YM155 inhibited ATC proliferation, reduced survivin and claspin expression, induced S-phase arrest, and reduced tumor growth and metastasis in vivo.
Conclusions:
- YM155 demonstrates significant anticancer activity against anaplastic thyroid cancer.
- Survivin is a validated therapeutic target in ATC.
- YM155 warrants clinical investigation as a potential treatment for advanced and metastatic ATC.
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