Anaplastic thyroid cancer: Genetic roles, targeted therapy, and immunotherapy

Anaplastic thyroid cancer (ATC) stands as the most formidable form of thyroid malignancy, presenting a persistent challenge in clinical management. Recent years have witnessed a gradual unveiling of the intricate genetic underpinnings governing ATC through next-generation sequencing. The emergence of this genetic landscape has paved the way for the exploration of targeted therapies and immunotherapies in clinical trials. Despite these strides, the precise mechanisms governing ATC pathogenesis and the identification of efficacious treatments demand further investigation. Our comprehensive review stems from an extensive literature search focusing on the genetic implications, notably the pivotal MAPK and PI3K-AKT-mTOR signaling pathways, along with targeted therapies and immunotherapies in ATC. Moreover, we screen and summarize the advances and challenges in the current diagnostic approaches for ATC, including the invasive tissue sampling represented by fine needle aspiration and core needle biopsy, immunohistochemistry, and ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography. We also investigate enormous studies on the prognosis of ATC and outline independent prognostic factors for future clinical assessment and therapy for ATC. By synthesizing this literature, we aim to encapsulate the evolving landscape of ATC oncology, potentially shedding light on novel pathogenic mechanisms and avenues for therapeutic exploration.