Eficacia de Vitrakvi (Larotrectinib) para el tratamiento de tumores sólidos portadores de genes NTRK y el impacto de las mutaciones TRKC

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Publicado: Apr 30, 2025
DOI: https://doi.org/10.17163/lgr.n42.2025.07
Palabras clave:
Vitrakvi, TRK, Cáncer sólido, NT-3, Mutación, Docking

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Ali Adel Dawood
Departamento de Anatomía, Escuela de Medicina, Universidad de Mosul, Mosul, Iraq. [https://ror.org/039cf4q47]
https://orcid.org/0000-0001-8988-5957

Resumen

Vitrakvi es un tratamiento oncológico dirigido a tumores sólidos que presentan fusiones génicas del gen NTRK. Las alteraciones en los genes NTRK constituyen efectos genéticos poco comunes que pueden manifestarse en tumores originados en diversos órganos, incluidos los pulmones, las glándulas tiroideas y el intestino. El objetivo de este estudio fue identificar el sitio de unión de Vitrakvi a las quinasas del receptor de tropomiosina (TRK), así como evaluar los efectos de las mutaciones en TRKC sobre el sitio de fusión. Para obtener la estructura química de Vitrakvi se utilizaron recursos como PubChem, y la estructura tridimensional de las TRK se obtuvo del Protein Data Bank (PDB). El acoplamiento molecular (docking) se llevó a cabo mediante el programa AutoDock Vina. Las simulaciones de acoplamiento, visualización y reconstrucción de las secuencias se realizaron utilizando los programas PyMol, BIOVIA y PyRx. La fusión de Vitrakvi con TRKA y TRKB se ve modificada cuando estas quinasas se combinan con sus respectivos estimuladores (BDGF y NT-4/5). En el caso de TRKC, la unión con Vitrakvi ocurre en la misma cadena que se acopla a su estimulador (NT-3); sin embargo, el sitio de fusión se desplaza respecto al sitio de la triple mutación. Aunque los ensayos clínicos con inhibidores de TRK se encuentran en fases iniciales, existen fundamentos prometedores para la esperanza tanto en pacientes con mutaciones en TRK como en el campo de las terapias dirigidas molecularmente.

Detalles del artículo

Número
2025: Acceso anticipado
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Artículo Científico
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