Anaplastic thyroid carcinoma (ATC) is the rarest and most aggressive form of thyroid cancer, marked by a poor prognosis and resistance to conventional treatments. Like many malignancies, ATC has a complex genetic landscape, with numerous mutations driving tumor initiation, progression, and therapeutic resistance. However, recent advances in molecular research have expanded our understanding of these genetic alterations, paving the way for new targeted treatment strategies. Currently, therapies targeting specific genetic mutations, such as BRAF and MEK, show promise, but their effectiveness is limited to patients harboring these mutations. To explore broader therapeutic possibilities, we conducted a comprehensive literature review using the PubMed database and Google to identify studies on key genetic mutations in ATC. By leveraging these molecular insights, we aim to highlight potential therapeutic avenues that could enhance treatment options and improve patient outcomes.

Papillary thyroid cancer (PTC) is the most common thyroid malignancy, with significant racial/ethnic disparities in incidence and survival. Asians have the highest incidence, and recurrence, while African Americans experience the lowest survival rates, suggesting contributions from genetic, environmental, and healthcare-related factors. While socioeconomic disparities play a role, emerging evidence highlights genetic and molecular mechanisms underlying these differences. This study examines differentially expressed genes (DEGs) to identify potential molecular drivers of PTC disparities. Bulk RNA-sequencing (RNA-seq) data from 20 PTC tumors (5 White, 5 African American, 5 Hispanic, and 5 Asian) were analyzed using the UseGalaxy platform. Preprocessing included quality control, adapter trimming, and genome alignment. Differential expression analysis identified genes with p < 0.01 and fold change ≥ 2.5. Volcano plots visualized significant DEGs. Gene Set Enrichment Analysis (GSEA) via eVITTA identified enriched pathways. TCGA data analysis validated racial/ethnic differences in gene expression. Ethnic groups exhibited distinct gene expression profiles. GSEA revealed differences in cell proliferation, immune regulation, and thyroid hormone metabolism. African Americans showed immune suppression and reduced tumor suppressor activity, while Asians exhibited enriched cell cycle and DNA repair pathways. Significant differences were confirmed in some of the genes in TCGA data analysis. This study identifies genetic factors contributing to racial disparities in PTC, emphasizing the need for further validation in larger cohorts and functional studies. Understanding these molecular differences may inform personalized treatment strategies and improve PTC outcomes across diverse populations.

Anaplastic thyroid carcinoma (ATC) is the rarest and most aggressive form of thyroid cancer, marked by a poor prognosis and resistance to conventional treatments. Like many malignancies, ATC has a complex genetic landscape, with numerous mutations driving tumor initiation, progression, and therapeutic resistance. However, recent advances in molecular research have expanded our understanding of these genetic alterations, paving the way for new targeted treatment strategies. Currently, therapies targeting specific genetic mutations, such as BRAF and MEK, show promise, but their effectiveness is limited to patients harboring these mutations. To explore broader therapeutic possibilities, we conducted a comprehensive literature review using the PubMed database and Google to identify studies on key genetic mutations in ATC. By leveraging these molecular insights, we aim to highlight potential therapeutic avenues that could enhance treatment options and improve patient outcomes.

Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), is widely prescribed for type 2 diabetes and obesity. Rodent studies showed thyroid C-cell tumors, prompting a boxed warning for medullary thyroid carcinoma (MTC); whether this extends to papillary thyroid carcinoma (PTC), a follicular-cell-derived tumor, is uncertain. This narrative review examines semaglutide and other GLP-1RAs in relation to PTC, distinguishing semaglutide-specific from class-level evidence, and PTC from differentiated thyroid cancer (DTC), MTC, and thyroid cancer overall. Most human studies evaluated GLP-1RAs as a class and reported thyroid cancer overall; semaglutide-specific and PTC-specific estimates are scarce. Pooled trials and national cohorts mostly showed no statistically significant increase in thyroid cancer, although three separate meta-analyses of randomized trials each reported a statistically significant increase in overall thyroid cancer, and case-control and spontaneous-reporting studies reported signals vulnerable to detection bias and confounding. In a matched cohort of 1072 patients with DTC, GLP-1RA exposure (median 16 months) was not significantly associated with progression over 69 months. Receptor-expression findings were inconsistent, and preclinical data did not show proliferative effects. The cohort and progression findings indicate no statistically detectable increase within the available sample sizes, exposure durations, and event numbers; they do not establish oncological safety. Semaglutide-specific, histology-resolved studies with longer exposure are needed.

Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA) marketed as Ozempic and Wegovy, is now among the most widely prescribed medications for type 2 diabetes and obesity. Rodent carcinogenicity studies demonstrated dose- and duration-dependent thyroid C-cell tumors, prompting a boxed warning for medullary thyroid carcinoma (MTC) and multiple endocrine neoplasia type 2 (MEN2), but whether this concern extends to papillary thyroid carcinoma (PTC), a follicular-cell-derived malignancy with distinct biology, remains uncertain. This narrative review evaluates current evidence on semaglutide and PTC, examining incidence, progression in patients with existing disease, receptor expression and mechanistic data, pharmacovigilance signals, sex-based patterns, and case reports published through August 2026. A pooled analysis of 93 trials (101,732 participants) and several national cohort studies found no statistically significant increase in thyroid cancer risk, and a matched cohort of 1072 patients with existing differentiated thyroid cancer found no association between GLP-1RA exposure and structural progression over a median of 69 months. A French case-control study and two FAERS disproportionality analyses reported elevated risk signals subject to detection bias and confounding by obesity. Receptor expression and functional studies were inconsistent but did not generally support a proliferative effect of GLP-1R agonism on PTC cells. Taken together, current evidence does not support semaglutide as a driver of PTC incidence or progression, though this remains an area warranting further prospective, subtype-specific study.

Background/Objectives: Thyroid cancer, predominantly papillary thyroid carcinoma (PTC), is diagnosed about three times more often in women than in men, yet in several cohorts male sex is associated with worse outcomes after diagnosis. We critically appraised this “female incidence–male outcome paradox” and evaluated non-coding RNA (ncRNA) as a candidate regulatory layer. Methods: We conducted a narrative review with documented search methods and an evidence table, complemented by an exploratory, covariate-adjusted analysis of CD274 and ACTA2 transcripts in The Cancer Genome Atlas thyroid carcinoma cohort (497 tumors; 58 normal samples). Results: Similar prevalence of subclinical PTC at autopsy in both sexes supports detection bias as the main driver of the female excess in incidence. Among diagnosed patients, male sex was associated with cancer-specific mortality in a large registry (adjusted HR 1.46, 95% CI 1.26–1.69) but not in several other cohorts; in a multicenter cohort, this association was confined to BRAF V600E-positive disease. In TCGA, ACTA2 was higher in male tumors after adjustment (fold difference 1.22, 95% CI 1.06–1.41), whereas lower CD274 in men was also present in normal thyroid. Sex-stratified androgen receptor–miR-146b correlations have been reported, but formal tests of sex-dependent effect modification are lacking. Conclusions: The paradox reflects detection-driven differences in incidence and a heterogeneous, mechanistically unresolved outcome association in men. The evidence supports sex-stratified studies with formal interaction testing, not sex-specific management.