Related Experiment Video
Updated: Mar 24, 2026
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
Carfilzomib potentiates CUDC-101-induced apoptosis in anaplastic thyroid cancer
Lisa Zhang1, Myriem Boufraqech1, Ross Lake2
1Endocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Abstract:
Anaplastic thyroid cancer (ATC) is one of the most aggressive human malignancies, with no effective treatment currently available. Previously, we identified agents active against ATC cells, both in vitro and in vivo, using quantitative high-throughput screening of 3282 clinically approved drugs and small molecules. Here, we report that combining two of these active agents, carfilzomib, a second-generation proteasome inhibitor, and CUDC-101, a histone deacetylase and multi-kinase inhibitor, results in increased, synergistic activity in ATC cells. The combination of carfilzomib and CUDC-101 synergistically inhibited cellular proliferation and caused cell death in multiple ATC cell lines harboring various driver mutations observed in human ATC tumors. This increased anti-ATC effect was associated with a synergistically enhanced G2/M cell cycle arrest and increased caspase 3/7 activity induced by the drug combination. Mechanistically, treatment with carfilzomib and CUDC-101 increased p21 expression and poly (ADP-ribose) polymerase protein cleavage. Our results suggest that combining carfilzomib and CUDC-101 would offer an effective therapeutic strategy to treat ATC.
Insights
Combining carfilzomib and CUDC-101 shows synergistic effects against anaplastic thyroid cancer (ATC). This drug combination effectively inhibits ATC cell proliferation and induces cell death, offering a potential new therapeutic strategy.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Anaplastic thyroid cancer (ATC) is a highly aggressive malignancy with limited therapeutic options.
- Previous research identified several clinically approved drugs and small molecules with activity against ATC cells.
Purpose of the Study:
- To investigate the synergistic effects of combining carfilzomib and CUDC-101 in treating anaplastic thyroid cancer.
- To evaluate the efficacy of this drug combination in inhibiting ATC cell proliferation and inducing cell death.
Main Methods:
- Quantitative high-throughput screening of 3282 clinically approved drugs and small molecules.
- Combination treatment of ATC cell lines with carfilzomib (proteasome inhibitor) and CUDC-101 (HDAC and multi-kinase inhibitor).
- Assessment of cellular proliferation, cell death, cell cycle arrest (G2/M), caspase 3/7 activity, p21 expression, and PARP cleavage.
Main Results:
- The combination of carfilzomib and CUDC-101 demonstrated synergistic inhibition of proliferation and induced cell death in multiple ATC cell lines.
- The drug combination synergistically enhanced G2/M cell cycle arrest and increased caspase 3/7 activity.
- Mechanistic studies revealed increased p21 expression and poly (ADP-ribose) polymerase (PARP) cleavage upon combination treatment.
Conclusions:
- Combining carfilzomib and CUDC-101 exhibits potent synergistic anti-ATC activity.
- This combination therapy represents a promising therapeutic strategy for anaplastic thyroid cancer.
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