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Un nuevo biomarcador TTF-1 optimiza el uso de inhibidores KRAS en cáncer de pulmón
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Investigadores del University of Texas M. D. Anderson Cancer Center identificaron la proteína TTF-1 (Thyroid Transcription Factor-1) como un biomarcador predictivo de supervivencia en pacientes con cáncer de pulmón no microcítico (NSCLC) avanzado portadores de la mutación KRAS G12C, tratados con el inhibidor dirigido sotorasib. Esta investigación publicada en Nature Medicine, analizó datos de 429 pacientes participantes en los ensayos clínicos CodeBreaK 100 y 200.
Los resultados evidencian que los pacientes con tumores de baja expresión de TTF-1 experimentan una mediana de supervivencia libre de progresión (SLP) de 2.8 meses y una supervivencia global (SG) de 4.5 meses tras el inicio del tratamiento con sotorasib. En contraste, aquellos con alta expresión de TTF-1 alcanzaron una SLP de 8.1 meses y una SG de 16 meses, posicionando a este biomarcador como un indicador clave para la estratificación y personalización terapéutica.
Este avance resulta especialmente relevante para Colombia, donde el cáncer pulmonar representa una carga significativa en salud pública y la incorporación de biomarcadores moleculares puede optimizar la selección terapéutica y mejorar los desenlaces clínicos.
Implicaciones terapéuticas del cáncer de pulmón: microambiente tumoral y biomarcadores líquidos
El estudio también reveló que el microambiente tumoral influye en la respuesta a sotorasib. Pacientes con tumores inmunológicamente “fríos”, caracterizados por ausencia de expresión del marcador PD-L1 y resistencia a la inmunoterapia, mostraron mejor respuesta al inhibidor KRAS comparado con la quimioterapia tradicional. Este hallazgo amplía las opciones terapéuticas para subgrupos con respuesta limitada a inmunoterapia, mejorando la equidad en el acceso a tratamientos efectivos.
Además, la rápida reducción del ADN tumoral circulante (ctDNA) fue identificada como un biomarcador dinámico y no invasivo para monitorear la eficacia terapéutica. En algunos pacientes, los niveles de ctDNA disminuyeron en tan solo ocho días desde el inicio del tratamiento, sugiriendo que pruebas sanguíneas periódicas podrían ayudar a ajustar la terapia en tiempo real y mejorar la toma de decisiones clínicas.
Estos avances fortalecen la implementación de la medicina personalizada en oncología pulmonar en Colombia, ofreciendo nuevas perspectivas para optimizar recursos, mejorar la supervivencia y diseñar estrategias combinadas para pacientes con pronóstico desfavorable.
Descargue aquí la investigación completa:
Nathalia Moreno González
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