The Impact of NF-κB-Mediated Cellular Plasticity Reprogramming on Anlotinib Sensitivity in Anaplastic Thyroid Carcinoma

Anaplastic thyroid carcinoma (ATC) is a highly aggressive form of thyroid cancer with limited treatment options. Anlotinib, a potent multi-target tyrosine kinase inhibitor, has shown significant anti-tumor effects in various types of cancer, including ATC. Our previous research has demonstrated that anlotinib effectively induces ferroptosis in ATC. However, the underlying mechanism influencing ferroptosis sensitivity remains incompletely understood. In our latest study, we have uncovered that thyroid cancer cells with different levels of differentiation display varying degrees of sensitivity to anlotinib. Additionally, we have observed that anlotinib treatment can upregulate NF-κB-mediated cellular plasticity reprogramming by using Western bolt and NF-κB pathway phosphorylation array. Intriguingly, inhibiting NF-κB can reverse cellular plasticity and enhance the efficacy of anlotinib in ATC cells, both in laboratory settings and animal models. This groundbreaking discovery illuminates the relationship between NF-κB signaling and cellular plasticity in determining ATC's response to anlotinib. The findings suggest that combining anlotinib with NF-κB inhibitors could lead to innovative treatment strategies for ATC.