Global analysis of actionable genomic alterations in thyroid cancer and precision-based pharmacogenomic strategies DOI Creative Commons

Samantha Espinoza-Ferrao,

Gabriela Echeverría‐Garcés, Sebastián Rivera-Orellana

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 14, 2025

Introduction Thyroid cancer, a prevalent endocrine malignancy, has an age-standardized incidence rate of 9.1 per 100,000 people and mortality 0.44 as 2024. Despite significant advances in precision oncology driven by large-scale international consortia, gaps persist understanding the genomic landscape thyroid cancer its impact on therapeutic efficacy across diverse populations. Methods To address this gap, we performed comprehensive data mining silico analyses to identify pathogenic variants driver genes, calculate allele frequencies, assess deleteriousness scores global populations, including African, Amish, Ashkenazi Jewish, East South Asian, Finnish non-Finnish European, Latino, Middle Eastern groups. Additionally, pharmacogenomic profiling, drug prescription, clinical trial were analyzed prioritize targeted strategies. Results Our analysis examined 56,622 40 cancer-driver genes 76,156 human genomes, identifying 5,001 known predicted oncogenic variants. Enrichment revealed critical pathways such MAPK, PI3K-AKT-mTOR, p53 signaling, underscoring their roles pathogenesis. High-throughput validation strategies confirmed actionable alterations RET, BRAF, NRAS, KRAS, EPHA7. Ligandability assessments identified these proteins promising targets. Furthermore, our findings highlight potential inhibitors, vandetanib, dabrafenib, selumetinib, for improving treatment outcomes. Discussion This study underscores significance integrating insights with disparities treatment. The identification population-specific targets provides foundation advancing oncology. Future efforts should focus underrepresented developing prevention strategies, fostering collaboration ensure equitable access testing innovative therapies. These initiatives have transform care align broader goals personalized medicine.

Language: Английский

Global analysis of actionable genomic alterations in thyroid cancer and precision-based pharmacogenomic strategies DOI Creative Commons

Samantha Espinoza-Ferrao,

Gabriela Echeverría‐Garcés, Sebastián Rivera-Orellana

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 14, 2025

Introduction Thyroid cancer, a prevalent endocrine malignancy, has an age-standardized incidence rate of 9.1 per 100,000 people and mortality 0.44 as 2024. Despite significant advances in precision oncology driven by large-scale international consortia, gaps persist understanding the genomic landscape thyroid cancer its impact on therapeutic efficacy across diverse populations. Methods To address this gap, we performed comprehensive data mining silico analyses to identify pathogenic variants driver genes, calculate allele frequencies, assess deleteriousness scores global populations, including African, Amish, Ashkenazi Jewish, East South Asian, Finnish non-Finnish European, Latino, Middle Eastern groups. Additionally, pharmacogenomic profiling, drug prescription, clinical trial were analyzed prioritize targeted strategies. Results Our analysis examined 56,622 40 cancer-driver genes 76,156 human genomes, identifying 5,001 known predicted oncogenic variants. Enrichment revealed critical pathways such MAPK, PI3K-AKT-mTOR, p53 signaling, underscoring their roles pathogenesis. High-throughput validation strategies confirmed actionable alterations RET, BRAF, NRAS, KRAS, EPHA7. Ligandability assessments identified these proteins promising targets. Furthermore, our findings highlight potential inhibitors, vandetanib, dabrafenib, selumetinib, for improving treatment outcomes. Discussion This study underscores significance integrating insights with disparities treatment. The identification population-specific targets provides foundation advancing oncology. Future efforts should focus underrepresented developing prevention strategies, fostering collaboration ensure equitable access testing innovative therapies. These initiatives have transform care align broader goals personalized medicine.

Language: Английский

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