Worldwide analysis of actionable genomic alterations in lung cancer and targeted pharmacogenomic strategies
Gabriela Echeverría-Garcés,
María José Ramos-Medina,
Ariana González,
Rodrigo Vargas,
Alejandro Cabrera-Andrade,
Isaac Armendáriz-Castillo,
Jennyfer M. García-Cárdenas,
David Ramírez-Sánchez,
Adriana Altamirano-Colina,
Paulina Echeverría-Espinoza,
María Paula Freire,
Belén Ocaña-Paredes,
Sebastián Rivera-Orellana,
Santiago Guerrero,
Luis A. Quiñones,
Andrés López-Cortés
Affiliations
Gabriela Echeverría-Garcés
Centro de Referencia Nacional de Genómica, Secuenciación y Bioinformática, Instituto Nacional de Investigación en Salud Pública “Leopoldo Izquieta Pérez”, Quito, Ecuador; Latin American Network for the Implementation and Validation of Clinical Pharmacogenomics Guidelines (RELIVAF-CYTED), Santiago, Chile
María José Ramos-Medina
German Cancer Research Center (DKFZ), Faculty of Biosciences, Heidelberg University, Heidelberg, Germany
Ariana González
Latin American Network for the Implementation and Validation of Clinical Pharmacogenomics Guidelines (RELIVAF-CYTED), Santiago, Chile; Dasa Genómica Latam, Buenos Aires, Argentina
Rodrigo Vargas
Latin American Network for the Implementation and Validation of Clinical Pharmacogenomics Guidelines (RELIVAF-CYTED), Santiago, Chile; Department of Molecular Biology, Galileo University, Guatemala City, Guatemala
Alejandro Cabrera-Andrade
Escuela de Enfermería, Facultad de Ciencias de la Salud, Universidad de Las Américas, Quito, Ecuador; Grupo de Bio-Quimioinformática, Universidad de Las Américas, Quito, Ecuador
Isaac Armendáriz-Castillo
Latin American Network for the Implementation and Validation of Clinical Pharmacogenomics Guidelines (RELIVAF-CYTED), Santiago, Chile
Jennyfer M. García-Cárdenas
Latin American Network for the Implementation and Validation of Clinical Pharmacogenomics Guidelines (RELIVAF-CYTED), Santiago, Chile; Laboratorio de Ciencia de Datos Biomédicos, Escuela de Medicina, Facultad de Ciencias Médicas de la Salud y de la Vida, Universidad Internacional del Ecuador, Quito, Ecuador
David Ramírez-Sánchez
Cancer Research Group (CRG), Faculty of Medicine, Universidad de Las Américas, Quito, Ecuador
Adriana Altamirano-Colina
Cancer Research Group (CRG), Faculty of Medicine, Universidad de Las Américas, Quito, Ecuador
Paulina Echeverría-Espinoza
Cancer Research Group (CRG), Faculty of Medicine, Universidad de Las Américas, Quito, Ecuador
María Paula Freire
Cancer Research Group (CRG), Faculty of Medicine, Universidad de Las Américas, Quito, Ecuador
Belén Ocaña-Paredes
Cancer Research Group (CRG), Faculty of Medicine, Universidad de Las Américas, Quito, Ecuador
Sebastián Rivera-Orellana
Cancer Research Group (CRG), Faculty of Medicine, Universidad de Las Américas, Quito, Ecuador
Santiago Guerrero
Latin American Network for the Implementation and Validation of Clinical Pharmacogenomics Guidelines (RELIVAF-CYTED), Santiago, Chile; Laboratorio de Ciencia de Datos Biomédicos, Escuela de Medicina, Facultad de Ciencias Médicas de la Salud y de la Vida, Universidad Internacional del Ecuador, Quito, Ecuador
Luis A. Quiñones
Latin American Network for the Implementation and Validation of Clinical Pharmacogenomics Guidelines (RELIVAF-CYTED), Santiago, Chile; Laboratory of Chemical Carcinogenesis and Pharmacogenetics, Department of Basic-Clinical Oncology (DOBC), Faculty of Medicine, University of Chile, Santiago, Chile; Department of Pharmaceutical Sciences and Technology, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Santiago, Chile
Andrés López-Cortés
Cancer Research Group (CRG), Faculty of Medicine, Universidad de Las Américas, Quito, Ecuador; Corresponding author.
Based on data from the Global Cancer Statistics 2022, lung cancer stands as the most lethal cancer worldwide, with age-adjusted incidence and mortality rates of 23.6 and 16.9 per 100,000 people, respectively. Despite significant strides in precision oncology driven by large-scale international research consortia, there remains a critical need to deepen our understanding of the genomic landscape across diverse racial and ethnic groups. To address this challenge, we performed comprehensive in silico analyses and data mining to identify pathogenic variants in genes that drive lung cancer. We subsequently calculated the allele frequencies and assessed the deleteriousness of these oncogenic variants among populations such as African, Amish, Ashkenazi Jewish, East and South Asian, Finnish and non-Finnish European, Latino, and Middle Eastern. Our analysis examined 117,707 variants within 86 lung cancer-associated genes across 75,109 human genomes, uncovering 8042 variants that are known or predicted to be pathogenic. We prioritized variants based on their allele frequencies and deleterious scores, and identified those with potential significance for response to anti-cancer therapies through in silico drug simulations, current clinical pharmacogenomic guidelines, and ongoing late-stage clinical trials targeting lung cancer-driving proteins. In conclusion, it is crucial to unite global efforts to create public health policies that emphasize prevention strategies and ensure access to clinical trials, pharmacogenomic testing, and cancer research for these groups in developed nations.