Advances in lenvatinib monotherapy and combination therapies in anaplastic thyroid cancer (Review)

Anaplastic thyroid cancer (ATC) is a highly malignant and aggressive endocrine tumor with the poorest prognosis among all thyroid cancer (TC) subtypes. Although ATC is extremely rare, treatment remains a notable challenge, as traditional therapies have exhibited very limited efficacy. Targeted small-molecule inhibitors that disrupt molecular signaling pathways offer a potential therapeutic approach for patients with ATC. Lenvatinib, a tyrosine kinase inhibitor, has emerged as a promising therapeutic agent, which targets various factors involved in angiogenesis and tumor progression, including vascular endothelial growth factor receptor, platelet-derived growth factor receptor α, fibroblast growth factor receptor and mast/stem cell growth factor receptor. Preclinical and clinical trials have demonstrated the efficacy of lenvatinib, both as monotherapy and in combination with other targeted therapy, chemotherapy, immunotherapy, warranting a comprehensive review of these studies. However, lenvatinib monotherapy was associated with a high incidence of adverse events (including hypertension, anorexia and proteinuria) and certain limitations, particularly drug resistance, emphasizing the need for optimized therapeutic strategies. In the present review, the efficacy and safety of lenvatinib monotherapy and combination therapies in the treatment of ATC were examined. Furthermore, the feasibility and limitations of different combination therapies were analyzed and compared. The present review aimed to provide insights into potential lenvatinib-based regimens that could enhance survival outcomes and improve the quality of life for patients with ATC in the future.