Antineoplastic and Immunomodulatory Effects of Cabozantinib in Continuous and Primary Human Anaplastic Thyroid Cancer Cells

  • Cancers (Basel). 2026 Jul 23;18(15):2379. doi: 10.3390/cancers18152379.
Giusy Elia  1 ,  Silvia Martina Ferrari  1 ,  Eugenia Balestri  1 ,  Chiara Botrini  1 ,  Francesca Ragusa  1 ,  Valeria Mazzi  1 ,  Licia Rugani  1 ,  Simona Piaggi  2 ,  Elena Catania Romizi  1 ,  Oriana Fabrazzo  1 ,  Eleonora Giorgetti  2 ,  Alessia Baglini  1 ,  Gilda Varricchi  3  4  5 ,  Camilla Virili  6 ,  Salvatore Ulisse  7 ,  Gabriele Materazzi  1 ,  Alessandro Antonelli  1 ,  Poupak Fallahi  2
Affiliations
  • 1. Department of Surgical, Medical and Molecular Pathology and Critical Area, University of Pisa, 56126 Pisa, Italy.
  • 2. Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy.
  • 3. Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, 80131 Naples, Italy.
  • 4. World Allergy Organization (WAO) Center of Excellence, 80131 Naples, Italy.
  • 5. Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council, 80131 Naples, Italy.
  • 6. Department of Medico-Surgical Sciences and Biotechnologies, Endocrinology Section, "Sapienza" University of Rome, 04100 Latina, Italy.
  • 7. Department of Surgery, "Sapienza" University of Rome, 00161 Rome, Italy.
PMID: 42588600 DOI: 10.3390/cancers18152379
Abstract

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.

Keywords
anaplastic thyroid cancer; cabozantinib; in vitro study; primary cell cultures.