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Perspectivas genómicas sobre la resistencia innata en el cáncer de pulmón de células no pequeñas mutante en fase
Hayoung Seong1,2,3, Soo Han Kim1,2, Mi-Hyun Kim1,2
1Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea.
Cancer research and treatment
|August 29, 2025
Resumen
Los perfiles genómicos del cáncer de pulmón de células no pequeñas (CPNP) en etapa temprana con mutaciones del EGFR muestran una heterogeneidad temprana. La menor frecuencia del alelo de la mutación del EGFR (VAF) en etapas tempranas sugiere que las alteraciones genéticas concurrentes pueden conducir a la resistencia innata a los inhibidores de la tirosina quinasa del EGFR (ITC).
Área de la Ciencia:
- En el campo de la oncología
- La genómica
- Biología molecular
Sus antecedentes:
- El perfil genómico completo del cáncer de pulmón de células no pequeñas (CPNP) en etapa temprana con mutaciones en el receptor del factor de crecimiento epidérmico (EGFR) no está bien establecido.
- Comprender las alteraciones genómicas tempranas es crucial para identificar los mecanismos de resistencia a los inhibidores de la EGFR-tirosina quinasa (ITC).
Objetivo del estudio:
- Investigar los perfiles genómicos del NSCLC mutante en EGFR en estadio temprano y avanzado.
- Identificar posibles mecanismos de resistencia innata a las TKI del EGFR en el NSCLC mutante en el EGFR.
Principales métodos:
- Análisis retrospectivo de los perfiles genómicos de 160 pacientes con CPNM mutante en el EGFR (100 en estadio temprano, 60 en estadio avanzado).
- La secuenciación dirigida de próxima generación (NGS, por sus siglas en inglés) se utilizó para evaluar las alteraciones genéticas concurrentes (AG), la carga mutacional tumoral (TMB, por sus siglas en inglés) y la frecuencia del alelo de la variante de mutación EGFR (VAF, por sus siglas en inglés).
Principales resultados:
- No hay diferencias significativas en la proporción de GA concurrentes o en la mediana de TMB entre el NSCLC en estadio temprano y avanzado.
- VAF mediana significativamente menor de mutaciones del EGFR en estadio temprano en comparación con el NSCLC en estadio avanzado (19,3% frente a 29,6%).
- La mutación del EGFR VAF aumentó significativamente con la progresión de la enfermedad, mientras que la TMB se mantuvo sin cambios.
Conclusiones:
- La heterogeneidad genómica en el NSCLC mutante en EGFR emerge temprano en la tumorigénesis.
- La mutación más baja del EGFR VAF en la etapa temprana de la enfermedad sugiere que los AG concurrentes pueden contribuir a la resistencia innata a las TKI del EGFR.
- Las terapias combinadas deben considerarse incluso en el NSCLC mutante EGFR en etapa temprana.
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