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Terapias dirigidas en el cáncer de las vías biliares: cuando la precisión se vuelve imprecisa
C J O'Rourke1, J V Schou2, J B Andersen1
1Biotech Research and Innovation Centre (BRIC), Department of Health and Medical Sciences, University of Copenhagen, Copenhagen.
ESMO gastrointestinal oncology
|February 6, 2026
Resumen
Las terapias dirigidas ofrecen beneficios para los cánceres avanzados de las vías biliares (BTC) con alteraciones específicas. Sin embargo, los mecanismos de resistencia limitan la respuesta del paciente, lo que requiere criterios moleculares refinados para una mejor selección del tratamiento y terapias de combinación.
Área de la Ciencia:
- Oncología
- Gastroenterología
- Biología Molecular
Sus antecedentes:
- Los cánceres avanzados de las vías biliares (BTC) muestran una promesa para las terapias dirigidas debido a alteraciones genéticas accionables.
- Los inhibidores del receptor del factor de crecimiento de fibroblastos (FGFR) y los inhibidores de la isocitrato deshidrogenasa 1 (IDH1) están aprobados para subtipos específicos de BTC.
- Un subconjunto de pacientes no responde a las terapias dirigidas, incluso con criterios molecularmente coincidentes, lo que indica necesidades insatisfechas.
Objetivo del estudio:
- Investigar los mecanismos moleculares subyacentes a la resistencia a las terapias dirigidas en los BTC avanzados.
- Identificar biomarcadores novedosos y refinar los criterios de selección de pacientes para tratamientos dirigidos.
- Explorar estrategias para superar la resistencia terapéutica y mejorar los resultados de los pacientes.
Principales métodos:
- Análisis de alteraciones genéticas (ADN) y no genéticas (transcripcionales, traduccionales, post-traduccionales) en redes de señalización.
- Identificación de biomarcadores de resistencia coexistentes en tumores de BTC.
- Correlación de perfiles moleculares con patrones de respuesta y resistencia terapéutica.
Principales resultados:
- Los BTC exhiben una dependencia oncogénica de las redes de señalización, no solo de genes individuales, lo que contribuye a la resistencia.
- La resistencia primaria está mediada por alteraciones en las vías aguas arriba, aguas abajo o paralelas a la alteración dirigida.
- La duración limitada de la respuesta sugiere mecanismos de resistencia complejos más allá del objetivo primario.
Conclusiones:
- El refinamiento de los criterios moleculares para incluir biomarcadores de resistencia es crucial para la selección de pacientes.
- La comprensión de los mecanismos de resistencia permitirá el desarrollo de terapias de combinación de próxima generación.
- La mejora de la estratificación de pacientes y las estrategias de combinación pueden maximizar los beneficios del tratamiento y prolongar la duración de la respuesta en los BTC.
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