ArticleFrontiers in pharmacology2025
Global analysis of actionable genomic alterations in thyroid cancer and precision-based pharmacogenomic strategies.
Article in Frontiers in pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: Thyroid cancer, a prevalent endocrine malignancy, has an age-standardized incidence rate of 9.1 per 100,000 people and a mortality rate of 0.44 per 100,000 as of 2024. Despite significant advances in precision oncology driven by large-scale international consortia, gaps persist in understanding the genomic landscape of thyroid cancer and its impact on therapeutic efficacy across diverse populations. Methods: To address this gap, we performed comprehensive data mining and Results: Our analysis examined 56,622 variants in 40 thyroid cancer-driver genes across 76,156 human genomes, identifying 5,001 known and predicted oncogenic variants. Enrichment analysis revealed critical pathways such as MAPK, PI3K-AKT-mTOR, and p53 signaling, underscoring their roles in thyroid cancer pathogenesis. High-throughput validation strategies confirmed actionable genomic alterations in RET, BRAF, NRAS, KRAS, and EPHA7. Ligandability assessments identified these proteins as promising therapeutic targets. Furthermore, our findings highlight the clinical potential of targeted drug inhibitors, including vandetanib, dabrafenib, and selumetinib, for improving treatment outcomes. Discussion: This study underscores the significance of integrating genomic insights with pharmacogenomic strategies to address disparities in thyroid cancer treatment. The identification of population-specific oncogenic variants and actionable therapeutic targets provides a foundation for advancing precision oncology. Future efforts should focus on including underrepresented populations, developing population-specific prevention strategies, and fostering global collaboration to ensure equitable access to pharmacogenomic testing and innovative therapies. These initiatives have the potential to transform thyroid cancer care and align with the broader goals of personalized medicine.
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