Cytotoxic Effects of Sorafenib, Lapatinib, and Bevacizumab, Alone and in Combination, on Medullary Thyroid Carcinoma Cells.

Background: Medullary thyroid carcinoma is a rare neuroendocrine tumor with limited therapeutic options, as current kinase inhibitors are often associated with significant toxicity and drug resistance. This study aimed to explore novel treatment strategies by testing targeted agents alone and in combination. Methods: Human medullary thyroid carcinoma TT cells with RET mutations were treated with Sorafenib, Lapatinib, and Bevacizumab. Cell proliferation was monitored in real time using the xCELLigence system, and apoptosis was assessed by flow cytometry. Results: Sorafenib and Lapatinib each showed strong, dose-dependent cytotoxic effects, with Lapatinib demonstrating the greatest potency. Bevacizumab alone exhibited minimal cytotoxic activity, but when combined with Sorafenib or Lapatinib it significantly enhanced their effects, even at concentrations that were only partially effective individually. The Lapatinib-Bevacizumab combination produced the most potent inhibition of cell viability, comparable to high-dose monotherapy. Conclusions: These findings suggest that combining kinase inhibitors with Bevacizumab may enhance antitumor activity, allow the use of lower drug doses, and overcome resistance, representing a promising therapeutic strategy for medullary thyroid carcinoma that warrants further investigation in clinical settings.