Utilizing Three-Dimensional Culture Methods to Improve High-Throughput Drug Screening in Anaplastic Thyroid Carcinoma

Anaplastic thyroid carcinoma (ATC) is the most aggressive endocrine neoplasm, with a median survival of just four to six months post-diagnosis. Even with surgical and chemotherapeutic interventions, the five-year survival rate is less than 5%. Although combination dabrafenib/trametinib therapy was r...

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Bibliographic Details
Published in:Cancers 2022-04, Vol.14 (8), p.1855
Main Authors: Bergdorf, Kensey, Bauer, Joshua A, Westover, David, Phifer, Courtney, Murphy, Barbara, Tyson, Darren R, Lee, Ethan, Weiss, Vivian L
Format: Article
Language:English
Subjects:
Antitumor agents
Bortezomib
Cancer therapies
Cell culture
Clinical trials
Drug development
Drug screening
Drugs
Spheroids
Thyroid cancer
Thyroid carcinoma
Tumors
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Summary:Anaplastic thyroid carcinoma (ATC) is the most aggressive endocrine neoplasm, with a median survival of just four to six months post-diagnosis. Even with surgical and chemotherapeutic interventions, the five-year survival rate is less than 5%. Although combination dabrafenib/trametinib therapy was recently approved for treatment of the ~25% of ATCs harboring mutations, there are no approved, effective treatments for -wildtype disease. Herein, we perform a screen of 1525 drugs and evaluate therapeutic candidates using monolayer cell lines and four corresponding spheroid models of anaplastic thyroid carcinoma. We utilize three-dimensional culture methods, as they have been shown to more accurately recapitulate tumor responses in vivo. These three-dimensional cultures include four distinct ATC spheroid lines representing unique morphology and mutational drivers to provide drug prioritization that will be more readily translatable to the clinic. Using this screen, we identify three exceptionally potent compounds (bortezomib, cabazitaxel, and YM155) that have established safety profiles and could potentially be moved into clinical trial for the treatment of anaplastic thyroid carcinoma, a disease with few treatment options.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers14081855