Biología molecular del cáncer de pulmón de célula no pequeña
Molecular biology of Non-small cell lung cancer
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Introducción: el cáncer de pulmón de célula no pequeña (NSCLC) representa aproximadamente el 85% de los casos de cáncer de pulmón y sigue siendo una causa principal de mortalidad por cáncer a nivel mundial, con una tasa de supervivencia global a 5 años de alrededor del 20%.
Métodos: se realizó una revisión narrativa de la literatura que sintetiza el conocimiento actual sobre la biología molecular del NSCLC, enfatizando las alteraciones genómicas, la evolución tumoral y las implicaciones terapéuticas, particularmente en el adenocarcinoma (LUAD) y el carcinoma de células escamosas (LUSC).
Resultados: se destacan diferencias clave entre fumadores y no fumadores, incluyendo una mayor carga mutacional y transversiones en fumadores, frente a alteraciones genómicas accionables (AGAs) como EGFR, KRAS, ALK y ROS1 en no fumadores. La revisión discute cambios somáticos en el ADN, perfiles de expresión de ARN, comutaciones, microambiente tumoral (TME), vesículas extracelulares y enfoques multiómicos que revelan la heterogeneidad tumoral y los mecanismos de resistencia. Los aspectos traslacionales cubren diagnósticos emergentes, como el ADN tumoral circulante y los exosomas, así como terapias, incluyendo inhibidores de tirosina quinasa (TKIs), inmunoterapia y estrategias novedosas dirigidas al microbioma y a las microvesículas.
Conclusiones: la caracterización molecular del NSCLC resulta de la máxima relevancia para la toma de decisiones terapéuticas más allá de la enfermedad avanzada; a pesar de los avances, persisten brechas, subrayando la necesidad de enfoques personalizados para lograr la curación en etapas tempranas y mejorar los resultados en enfermedad avanzada.
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