Related Experiment Video
Updated: Jun 22, 2025
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
Antineoplastic Effect of ALK Inhibitor Crizotinib in Primary Human Anaplastic Thyroid Cancer Cells with STRN-ALK
Silvia Martina Ferrari1, Francesca Ragusa2, Giusy Elia2
1Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy.
Abstract:
Anaplastic thyroid cancer (ATC) is one of the deadliest human cancers and represents <2% of thyroid carcinomas. A therapeutic target for ATC is represented by anaplastic lymphoma kinase (ALK) rearrangements, involved in tumor growth. Crizotinib is an oral small-molecule tyrosine kinase inhibitor of the ALK, MET, and ROS1 kinases, approved in ALK-positive non-small cell lung cancer. Until now, the effect of crizotinib in "primary human ATC cells" (pATCs) with transforming striatin (STRN)-ALK fusion has not been reported in the literature. In this study, we aimed to obtain pATCs with STRN-ALK in vitro and evaluate the in vitro antineoplastic action of crizotinib. Thyroid surgical samples were obtained from 12 ATC patients and 6 controls (who had undergone parathyroidectomy). A total of 10/12 pATC cultures were obtained, 2 of which with transforming STRN-ALK fusion (17%). Crizotinib inhibited proliferation, migration, and invasion and increased apoptosis in 3/10 pATC cultures (2 of which with/1 without STRN-ALK), particularly in those with STRN-ALK. Moreover, crizotinib significantly inhibited the proliferation of AF cells (a continuous cell line obtained from primary ATC cells). In conclusion, the antineoplastic activity of crizotinib has been shown in human pATCs (with STRN-ALK) in preclinical studies in vitro, opening the way to future clinical evaluation in these patients.
Insights
Crizotinib demonstrates significant anti-cancer effects in primary human anaplastic thyroid cancer (ATC) cells, particularly those with STRN-ALK fusion. This preclinical study supports crizotinib as a potential therapeutic option for advanced ATC.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- Anaplastic thyroid cancer (ATC) is a rare but highly aggressive malignancy with limited treatment options.
- Anaplastic lymphoma kinase (ALK) rearrangements are implicated in ATC pathogenesis and represent a potential therapeutic target.
- Crizotinib, an ALK inhibitor, is approved for ALK-positive non-small cell lung cancer but its efficacy in ATC is largely unexplored.
Purpose of the Study:
- To establish primary human ATC cells (pATCs) with STRN-ALK fusion in vitro.
- To evaluate the in vitro antineoplastic effects of crizotinib on pATCs, especially those harboring STRN-ALK fusion.
- To assess crizotinib's impact on proliferation, migration, invasion, and apoptosis in ATC models.
Main Methods:
- Surgical samples from 12 ATC patients and 6 controls were used to establish pATC cultures.
- Two out of ten established pATC cultures (17%) exhibited transforming STRN-ALK fusion.
- In vitro assays were performed to assess the effects of crizotinib on cell proliferation, migration, invasion, and apoptosis.
Main Results:
- Crizotinib significantly inhibited proliferation, migration, and invasion in 3/10 pATC cultures.
- Crizotinib demonstrated a notable increase in apoptosis in treated pATC cultures.
- The anti-neoplastic effects were particularly pronounced in pATC cultures with STRN-ALK fusion.
- Crizotinib also inhibited proliferation in the AF cell line derived from primary ATC.
Conclusions:
- Crizotinib exhibits preclinical anti-cancer activity in human pATCs with STRN-ALK fusion in vitro.
- These findings suggest crizotinib holds promise as a targeted therapy for a subset of ATC patients.
- Further clinical investigation of crizotinib in ATC patients with ALK rearrangements is warranted.
