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Heterogeneidad clonal y evolución tumoral: pasado, presente y futuro

Nicholas McGranahan¹, Charles Swanton²

¹Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, Paul O'Gorman Building, 72 Huntley Street, London WC1E 6BT, UK; Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, 1 Midland Rd, London NW1 1AT, UK.

|February 11, 2017

Resumen

La heterogeneidad intratumoral impulsa la evolución del cáncer y la resistencia a los medicamentos. Las nuevas estrategias terapéuticas dirigidas a la evolución del tumor y el microambiente son cruciales para mejorar los resultados de los pacientes.

Área de la Ciencia:

En el campo de la oncología
Biología evolutiva
La genética

Sus antecedentes:

La heterogeneidad intra-tumoral es un obstáculo significativo en la medicina del cáncer, promoviendo la evolución del tumor.
Comprender la dinámica de la evolución del tumor es fundamental para desarrollar terapias efectivas contra el cáncer.

Objetivo del estudio:

Revisar los datos y tecnologías actuales que aclaran la heterogeneidad intra-tumoral.
Para discutir la dinámica evolutiva, las limitaciones y las contingencias en el cáncer.
Para resaltar el papel de los saltos macroevolutivos y el microambiente del tumor.

Principales métodos:

Revisión de los datos existentes y de los avances tecnológicos en la investigación del cáncer.
Análisis de los principios evolutivos aplicados al desarrollo de tumores.
Examen de la influencia del microambiente tumoral en la heterogeneidad y la resistencia a los fármacos.

Principales resultados:

La heterogeneidad intra-tumoral es prevalente en varios tipos de cáncer.
Los saltos macroevolutivos, incluidas las alteraciones cromosómicas, son los principales impulsores de la evolución del tumor y la metástasis.
El microambiente tumoral contribuye significativamente a la heterogeneidad y al desarrollo de la resistencia a los medicamentos.

Conclusiones:

Se necesitan nuevos enfoques para el desarrollo de fármacos, centrados en las propiedades adaptativas del microambiente inmune.
Es esencial limitar las propiedades adaptativas del tumor y avanzar en el diseño de los ensayos clínicos.
Se pueden lograr mejores resultados para los pacientes mediante estrategias terapéuticas y de ensayo integradas.

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