Exosomes derived from human bone marrow mesenchymal stem cells (hBMSCs) containing PTCSC3 mitigate erlotinib resistance in lung adenocarcinoma cells through modulation of the Wnt/B-Catenin signaling pathway

Abstract

[ES] La resistencia adquirida a inhibidores de tirosina quinasa (TKIs), como el erlotinib, representa un desafío clínico importante en el tratamiento del adenocarcinoma pulmonar (LUAD). Este estudio evalúa el uso de exosomas derivados de células madre mesenquimales de médula ósea humana (hBMSCs), cargados con el ARN largo no codificante PTCSC3, como estrategia para revertir dicha resistencia. Los análisis funcionales mostraron una disminución en la actividad de β-catenina y de sus dianas oncogénicas, restaurando la sensibilidad al fármaco. Estos resultados proponen una nueva vía terapéutica basada en la modulación epigenética mediante exosomas, con potencial aplicación clínica previa validación in vivo.

[EN] Lung adenocarcinoma (LUAD) patients frequently develop resistance to tyrosine kinase inhibitors (TKIs), such as erlotinib, limiting treatment efficacy. In this study, we investigated the potential of exosomes derived from hBMSCs, loaded with the long non-coding RNA PTCSC3, to reverse erlotinib resistance. Functional assays revealed that these exosomes downregulated β-catenin and its downstream targets, restoring drug sensitivity in LUAD cells. Our findings highlight a novel therapeutic strategy using exosomal PTCSC3 to target the Wnt / β-Catenina signaling pathway and overcome acquired resistance. Further in vivo validation is needed to explore its clinical application.