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Aprovechar el microambiente tumoral como objetivo de las terapias contra el cáncer: una revisión de las oportunidades

Hakan Guven¹, Zoltán Székely^2,3,4,5

¹Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, 675 Hoes Lane West, Piscataway, NJ 08854, USA.

|August 28, 2025

Resumen

Las terapias contra el cáncer se enfrentan a desafíos del microambiente tumoral (EMT). Esta revisión explora los cambios dirigidos a TME para nuevas terapias como los conjugados anticuerpo-fármaco (ADC) y los conjugados de moléculas pequeñas (SMDC).

Área de la Ciencia:

En el campo de la oncología
La bioquímica
Desarrollo de drogas

Sus antecedentes:

Los tratamientos tradicionales contra el cáncer como la quimioterapia tienen limitaciones que incluyen índices terapéuticos estrechos y poca especificidad.
Las terapias avanzadas, como los conjugados de anticuerpos y fármacos (ADC), se enfrentan a desafíos como una baja penetración del tumor y altos costos de producción.
El microambiente tumoral (TME) presenta condiciones bioquímicas únicas que obstaculizan y ofrecen oportunidades para las terapias contra el cáncer.

Objetivo del estudio:

Revisar cinco parámetros clave del microambiente tumoral (EMT) que pueden ser objeto de tratamiento terapéutico.
Discutir la relevancia de estos parámetros de EMT para tipos específicos de cáncer y identificadores fenotípicos.
Examinar las fracciones químicas disponibles y las estrategias de diseño para explotar la dinámica de las EMT en el tratamiento del cáncer.

Principales métodos:

Revisión de la literatura centrada en el microambiente tumoral (EMT) y su impacto en el tratamiento del cáncer.
Análisis de cinco parámetros específicos de la EMT: niveles de oxígeno, pH, actividad enzimática, expresión de antígeno superficial y composición del estroma.
Examen de las estrategias terapéuticas, incluidos los conjugados anticuerpo-medicamento (ADC), los conjugados de moléculas pequeñas (SMDC) y los prodrogas.

Principales resultados:

Los tumores sólidos sufren cambios microambientales significativos a medida que crecen, creando objetivos terapéuticos únicos.
Los parámetros específicos de TME se pueden orientar utilizando varios sistemas de administración de fármacos como ADC y SMDC.
La revisión proporciona un marco para el diseño de terapias que explotan las características de la EMT.

Conclusiones:

El microambiente tumoral (TME) ofrece características explotables para el desarrollo de terapias contra el cáncer novedosas y más efectivas.
Dirigirse a parámetros específicos de EMT puede superar las limitaciones de los tratamientos contra el cáncer tradicionales y avanzados.
Comprender la dinámica de la EMT es crucial para el diseño de terapias contra el cáncer de próxima generación.

Palabras clave:

Conjugado de anticuerpos y fármacos Efecto espectador el cáncer diseño de fármacos hipoxia Pro-medicamentos Conjugado de moléculas pequeñas toxicidad sistémica microambiente del tumor

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