Targeted therapy and drug resistance in thyroid cancer

Thyroid cancer is the most common endocrine malignancy, the incidence of which has increased significantly over the past decades. Advanced thyroid cancers, especially locally advanced or metastatic poorly differentiated thyroid cancer and anaplastic thyroid cancer, also show increased incidence and mortality rate. The treatment of advanced thyroid cancer has undergone rapid evolution in the last decade, with multiple kinase inhibitor drug approvals for each subtype of thyroid cancer. However, the drug efficacy in those patients is not satisfying owing to primary and secondary drug resistance. Hence, a full comprehension of the underlying mechanisms is worth discussing. In this review, we introduce the clinical application of existing kinase inhibitors that are recommended for patients with advanced thyroid cancer and discuss several significant resistance mechanisms, including key signaling pathway regulation, the tumor microenvironment, ABC transporters, epithelial-tomesenchymal transition and cancer stem-like cells, apoptosis, autophagy, and aerobic glycolysis. Understanding the molecular basis of drug resistance in thyroid cancer will be helpful for the enhancement of drug combination therapy and promoting the development of new drugs against advanced thyroid cancer.

Automated summary

This review focuses on the rapid development of treatment for advanced thyroid cancer and the study of drug resistance mechanisms. The current treatment for advanced thyroid cancer is not satisfactory due to the existence of drug resistance. Understanding the mechanisms of drug resistance in thyroid cancer is crucial for improving the effectiveness of combination therapy and promoting the development of new drugs.