Targeted Therapy for Anaplastic Thyroid Carcinoma: Advances and Management

SIMPLE SUMMARY: The exceedingly aggressive and rare tumor, anaplastic thyroid carcinoma, is generally resistant to traditional antitumor therapies. In recent years, targeted therapy has become a hot research topic, giving patients with this malignant disease great hope. Therefore, it is necessary to review these studies and summarize the efficacy and adverse effects of various types of targeted drugs, not only to provide practical information for future basic research on related targeted drugs but also to help clinicians understand the research advances and management of these drugs in order to make the best clinical treatment recommendations for patients. ABSTRACT: Anaplastic thyroid carcinoma (ATC) is a rare and highly fatal cancer with the worst prognosis of all thyroid carcinoma (TC) histological subtypes and no standard treatment. In recent years, the explosion of investigations on ATC-targeted agents has provided a new treatment strategy for this malignant condition, and a review of these studies is warranted. We conducted a comprehensive literature search for ATC-targeted drug studies and compiled a summary of their efficacy and adverse effects (AEs) to provide new insights. Multiple clinical trials have demonstrated the efficacy and safety of dabrafenib in combination with trametinib for the treatment of ATC, but vemurafenib and NTRK inhibitors showed limited clinical responses. We found that the previously valued therapeutic effect of lenvatinib may be unsatisfactory; combining tyrosine kinase (TK) inhibitors (TKIs) with other agents results in a higher rate of clinical benefit. In addition, specific medications, including RET inhibitors, mTOR inhibitors, CDK4/6 inhibitors, and Combretastatin A4-phosphate (CA4P), offer tremendous therapeutic potential. The AEs reported for all agents are relatively numerous but largely manageable clinically. More clinical trials are expected to further confirm the effectiveness and safety of these targeted drugs for ATC.