Antineoplastic Activity of Pazopanib in Anaplastic Thyroid Cancer in Primary Culture

Int J Mol Sci. 2023 Jan 25;24(3):2398. doi: 10.3390/ijms24032398.

Abstract

Anaplastic thyroid cancer (ATC) is a rare and rapidly fatal human cancer. Its usual treatment includes the combination of surgery, external hyperfractionated radiation therapy, and chemotherapy. These treatments permit achieving about 6-10 months of median survival. For this reason, it is challenging to predict the ATC patient clinical therapy responsiveness. Pazopanib is a multitarget tyrosine kinase inhibitor of VEGF receptors, PDGF, and c-Kit. Until now, the effect of pazopanib in primary human ATC cells (pATC) has not been reported in the literature. The aim of our study was to evaluate in vitro the antineoplastic effect of pazopanib in pATC. Surgical thyroidal tissues were collected from five patients with ATC, from thyroid biopsy at the moment of first surgical operation. An inhibition of proliferation, migration, and invasion, and an increase in apoptosis were demonstrated upon treating pATC cells with pazopanib (p < 0.05). Moreover, pazopanib was able to significantly decrease the VEGF expression in pATC cells (p < 0.05). To conclude, in this study, we demonstrate the antineoplastic activity of the antiangiogenic inhibitor, pazopanib, in human pATC in vitro.

Keywords: anaplastic thyroid cancer; apoptosis; invasion; migration; pazopanib; primary cell cultures; proliferation; tyrosine kinase inhibitors.

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Humans
  • Thyroid Carcinoma, Anaplastic* / pathology
  • Thyroid Neoplasms* / pathology
  • Vascular Endothelial Growth Factor A / therapeutic use

Substances

  • 4-anisoyl-3-(1,2,2-trimethylcyclopentane carboxylic acid)
  • pazopanib
  • Vascular Endothelial Growth Factor A
  • Antineoplastic Agents

Grants and funding

This research received no external funding.