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Nuevos avances en la comprensión de los mecanismos y los desafíos del tratamiento de la resistencia a la terapia

Mengle Long^1,2,3, Shixuan Peng^1,2,3, Qingyang Wen^1,2

¹Department of Oncology, Graduate Collaborative Training Base of The First People's Hospital of Xiangtan City, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China.

Cancer drug resistance (Alhambra, Calif.)

|August 28, 2025

Resumen

La resistencia terapéutica a los inhibidores de la tirosina quinasa del linfoma anaplásico (ALK-TKIs) es un obstáculo significativo en el tratamiento del cáncer de pulmón de células no pequeñas (NSCLC) positivo para ALK. Comprender los mecanismos de resistencia es crucial para desarrollar nuevas estrategias para mejorar los resultados de los pacientes.

Área de la Ciencia:

En el campo de la oncología
Biología molecular
Farmacología

Sus antecedentes:

La reorganización de la linfoma quinasa anaplásica (ALK) es un factor clave en el cáncer de pulmón de células no pequeñas (CPNPC), que conduce a terapias dirigidas.
A pesar de los avances en los inhibidores de la tirosina quinasa (ITC) de ALK, la resistencia terapéutica sigue siendo un desafío clínico significativo.
Tanto los mecanismos on-target como los off-target contribuyen a la resistencia adquirida, lo que requiere una mayor investigación.

Objetivo del estudio:

Revisar los conocimientos actuales sobre los mecanismos de resistencia a la terapia dirigida a ALK en el cáncer de pulmón.
Discutir las estrategias de tratamiento y los avances terapéuticos recientes para superar la resistencia.
Explorar el impacto del sistema inmune y el microambiente tumoral en la resistencia a ALK-TKI.

Principales métodos:

Revisión de la literatura de los estudios sobre la resistencia a las ALK-TKI en el CPNM.
Análisis de los mecanismos de resistencia primaria y adquirida.
Síntesis de información sobre el manejo clínico y las terapias emergentes.

Principales resultados:

La resistencia a los ALK-TKIs, incluidas las generaciones más nuevas, surge con frecuencia durante el tratamiento.
Diversos eventos moleculares, tanto en el objetivo como fuera del objetivo, subyacen al fracaso del tratamiento.
El microambiente tumoral y las respuestas inmunes juegan un papel en el desarrollo de la resistencia.

Conclusiones:

Una comprensión completa de la resistencia a la terapia dirigida a ALK es esencial para desarrollar nuevas estrategias de tratamiento.
Se necesitan más investigaciones para aclarar los mecanismos complejos de resistencia y orientar el tratamiento clínico.
Los conocimientos mejorados ayudarán en el diagnóstico y tratamiento de pacientes con cáncer de pulmón ALK-positivo resistente.

Palabras clave:

Sin embargo, no se debe tomar en consideración el riesgo de cáncer de pulmón.Mecanismos de resistencia a las drogas microambiente inmunológico mutaciones transformación de células pequeñas tratamiento dirigido

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