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.

Autoimmune thyroid diseases (AITDs) represent T cell-mediated, organ-specific autoimmune disorders caused by immune dysregulation, culminating in an immune-mediated attack on thyroid tissue. AITD etiopathogenesis is the result of the interplay between a genetic susceptibility and environmental factors; hypothyroidism and thyrotoxicosis are the respective clinical hallmarks of autoimmune thyroiditis and Graves’disease, the two main forms of AITD. The application of nanomedicine in the context of thyroid disorders ranges from nanodiagnosis and nanotherapy to nanotheranostics. Nanomedicine has been used to develop new sensitive methods for the determination of the TSH, iodine and TSAb. Furthermore, other studies have used nanomedicine to explore new treatments of autoimmune thyroiditis, Graves’disease and also thyroid eye disease. In the future, the application of nanomedicine will be personalized in accordance with individual genetic profiles, thus improving the therapeutic effectiveness and reducing the undesirable side effects with improved patient outcomes.

Background/Objectives: To date, the antineoplastic effect of cabozantinib in in vitro anaplastic thyroid cancer (ATC) cells has not yet been investigated. We aim to evaluate the antineoplastic and immunomodulatory effect of cabozantinib in both primary and continuous ATC cell cultures in vitro. Methods: The antineoplastic activity of cabozantinib was evaluated in ATC cell lines (8305C; CAL62) and in five different primary ATC cells obtained directly from patients. Results: Increasing concentrations of cabozantinib were tested showing a significant decrease in viability/proliferation and an increase in apoptosis in the treated cells vs. control. A scratch assay was also performed to evaluate the effect of cabozantinib on migration showing a significant inhibition of it vs. control. Moreover, we showed a decrease in the secretion of both CXCL10 and CCL2 (T-helper (Th)1 and (Th)2 chemokines) under the treatment with cabozantinib, thus suggesting an immunomodulatory effect of the drug. Conclusions: A personalized approach for each patient can be achieved by using primary human ATC cells obtained directly from the patient, since in vitro studies permit assessing the chemosensitivity of cells obtained from each subject. These results in our opinion are very promising for a future in vivo evaluation of cabozantinib in patients with ATC.