Thyroid Gland Anaplastic Carcinoma

Emerging data also indicate that reverse transcriptase inhibitors (e.g., lamivudine, nevirapine) can partially suppress retroelement activity, induce transcriptional reprogramming and restore radioiodine uptake in refractory thyroid tumors, highlighting a potential therapeutic vulnerability. By integrating cancer epigenetics and mobilome biology, this review reframes thyroid tumor evolution as a process shaped not only by genetic alterations but also by retroelement-mediated disruption of genome regulation. Retroelements may serve as biomarkers of aggressive transformation and as actionable targets in translational oncology.

Preclinical studies show that pharmacological inducers, including vitamin C, tenacissoside H, neferine, curcumin, and shikonin, as well as targeted agents such as dabrafenib and anlotinib, can trigger or synergize with ferroptosis. Although systemic toxicity and resistance remain obstacles, biomarker-driven selection and drug repurposing offer promise. Ferroptosis represents a mechanistically distinct and clinically exploitable pathway for ATC.

PD-L1 expression defines a biologically and clinically relevant subset of ATCs with distinct immune features and therapeutic vulnerabilities. Standardizing PD-L1 testing and integrating it with molecular and microenvironmental biomarkers will be essential to refine patient selection for immunotherapy and combination strategies, improving outcomes.

In thyroid tissue, genes related to immune response and metabolic processes, are regulated by TFs in an age- and sex-biased manner. These age- and sex-specific gene regulatory variations may contribute to the variation in risk of thyroid conditions with age and an overall higher risk of diseases in females compared to males, thus emphasizing the need for tailored screening and prevention strategies.

Contemporary thyroid cancer BrM outcomes are dependent on primary malignancy histology and may benefit from further molecular profiling.

WTAP regulated the m6A modification and mRNA stability of PRMT1. The WTAP/PRMT1 signaling axis modulated cuproptosis, thereby influencing ATC progression. These findings highlighted the potential of targeting the WTAP/PRMT1 pathway as a therapeutic strategy for ATC.

Collectively, these findings identify Nrf2 as a pivotal driver of ATC anoikis resistance and metastatic competence through regulation of the BCL-2/SLC7A11 axis. Targeting the Nrf2-dependent survival pathway may thus offer a promising therapeutic strategy for this otherwise refractory malignancy.

P2, N=30, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Nov 2025 --> Nov 2027 | Trial primary completion date: Nov 2025 --> Nov 2027

At the level of a single cell, the adapted cells, caught in the act of moving, showed high-level expressions of vimentin (VIM), fibronectin (FN), and N-cadherin. High-level ER stress acts as a selection factor favoring the emergence of a cell population showing "mesenchymal drift" with a more malignant phenotype.

P1, N=6, Recruiting, City of Hope Medical Center | Trial completion date: Oct 2025 --> Feb 2026 | Trial primary completion date: Oct 2025 --> Feb 2026

Understanding the genetic landscape of thyroid carcinoma of follicular cells is essential to optimize clinical management and to identify molecular targets to treat cases with aggressive disease refractory to standard radioactive iodine therapy. What follows is a comprehensive and updated outline of the main somatic genetic and molecular alterations in thyroid carcinoma of follicular cells.

New technologies, including single-cell RNA sequencing and spatial transcriptomics, will improve understanding of heterogeneous lncRNA-microRNA networks in TC and support precision medicine. LncRNAs signify both molecular drivers and clinical targets for thyroid cancer.