Tumor microenvironment-guided targeted and immunotherapy in anaplastic thyroid cancer: a literature review from preclinical models to clinical translation

Background and Objective: Anaplastic thyroid cancer (ATC) is among the most aggressive human malignancies, with a median survival of 3-6 months. The tumor microenvironment (TME) drives progression and therapeutic resistance. We provide a narrative literature review integrating preclinical and clinical advances in TME-guided targeted therapy and immunotherapy. Methods: We systematically searched PubMed and Web of Science Core Collection for English-language studies on ATC TME, targeted therapy, and immunotherapy (January 2020-August 2025). Search strategies combined Medical Subject Headings (MeSH) terms and free-text keywords. We included preclinical and clinical original research while excluding reviews, editorials, and conference abstracts. Key Content and Findings: -mutant disease, BRAF/mitogen-activated protein kinase (MEK) inhibitors plus immune checkpoint inhibitors extended median survival from 9 to 17 months, with neoadjuvant reporting reaching 63 months. For non-targetable mutations, anti-angiogenic tyrosine kinase inhibitors (TKIs) plus immunotherapy achieved 66% complete response rates. TME-guided neoadjuvant combinations converted 38.9% of unresectable cases to resectable disease. Conclusions: This review provides clinicians with decision-making frameworks for TME-based treatment selection and identifies future research directions. Future directions include TME-stratified trials, biomarker standardization, and development of streamlined treatment algorithms to translate these advances into routine practice.