Local and systemic inflammatory and immune pathways in anaplastic thyroid carcinoma: emerging therapeutic targets.

Anaplastic thyroid cancer (ATC) is a rare endocrine cancer and one of the most lethal malignancies with only few treatment options. Most patients present with advanced and unresectable disease, and the median survival is approximately three months. In recent years, systemic treatments have become available for a subgroup of patients with ATC harboring targetable variants, such as BRAF/MEK inhibitors for patients with pathogenetic BRAF variants. However, only a small proportion of patients with ATC are eligible for these treatments, and most treated patients develop resistant and progressive disease. Hence, an urgent need remains for new treatment approaches. Accumulating evidence underlines the roles of systemic inflammation, immunosuppressive and protumoral immune cells tumor infiltration, and elevated numbers of circulating proinflammatory myeloid immune cells in tumor angiogenesis, metastasis, and disease progression of ATC. In this review, we highlight recent advances in understanding the pathogenesis of ATC and summarize latest trends in systemic treatments for patients with ATC. Moreover, based on these developments in understanding the pathophysiology of the disease, we propose how targeting different protumoral processes could lead to future treatment modalities for patients with ATC, with a specific focus on inflammatory processes and the innate immune system.

Copyright © 2026 The Authors. Published by Elsevier Ltd.. All rights reserved.

PMID: 43019925