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Gastric cancer actionable genomic alterations across diverse populations worldwide and pharmacogenomics strategies based on precision oncology.

Authors :
Echeverría-Garcés, Gabriela
Ramos-Medina, María José
Vargas, Rodrigo
Cabrera-Andrade, Alejandro
Altamirano-Colina, Adriana
Freire, María Paula
Montalvo-Guerrero, Juliana
Rivera-Orellana, Sebastián
Echeverría-Espinoza, Paulina
Quiñones, Luis A.
López-Cortés, Andrés
Source :
Frontiers in Pharmacology; 2024, p1-14, 14p
Publication Year :
2024

Abstract

Introduction: Gastric cancer is one of the most prevalent types of cancer worldwide. The World Health Organization (WHO), the International Agency for Research on Cancer (IARC), and the Global Cancer Statistics (GLOBOCAN) reported an age standardized global incidence rate of 9.2 per 100,000 individuals for gastric cancer in 2022, with a mortality rate of 6.1. Despite considerable progress in precision oncology through the efforts of international consortia, understanding the genomic features and their influence on the effectiveness of anti-cancer treatments across diverse ethnic groups remains essential. Methods: Our study aimed to address this need by conducting integrated in silico analyses to identify actionable genomic alterations in gastric cancer driver genes, assess their impact using deleteriousness scores, and determine allele frequencies across nine global populations: European Finnish, European non-Finnish, Latino, East Asian, South Asian, African, Middle Eastern, Ashkenazi Jewish, and Amish. Furthermore, our goal was to prioritize targeted therapeutic strategies based on pharmacogenomics clinical guidelines, in silico drug prescriptions, and clinical trial data. Results: Our comprehensive analysis examined 275,634 variants within 60 gastric cancer driver genes from 730,947 exome sequences and 76,215 whole-genome sequences from unrelated individuals, identifying 13,542 annotated and predicted oncogenic variants. We prioritized the most prevalent and deleterious oncogenic variants for subsequent pharmacogenomics testing. Additionally, we discovered actionable genomic alterations in the ARID1A, ATM, BCOR, ERBB2, ERBB3, CDKN2A, KIT, PIK3CA, PTEN, NTRK3, TP53, and CDKN2A genes that could enhance the efficacy of anti-cancer therapies, as suggested by in silico drug prescription analyses, reviews of current pharmacogenomics clinical guidelines, and evaluations of phase III and IV clinical trials targeting gastric cancer driver proteins. Discussion: These findings underline the urgency of consolidating efforts to devise effective prevention measures, invest in genomic profiling for underrepresented populations, and ensure the inclusion of ethnic minorities in future clinical trials and cancer research in developed countries. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
16639812
Database :
Complementary Index
Journal :
Frontiers in Pharmacology
Publication Type :
Academic Journal
Accession number :
177299246
Full Text :
https://doi.org/10.3389/fphar.2024.1373007