Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/173471
Title: | Inhibition of DDR1 enhances in vivo chemosensitivity in KRAS-mutant lung adenocarcinoma |
Author: | Nokin, Marie-Julie Darbo, Elodie Travert, Camille Drogat, Benjamin Lacouture, Aurélie San José, Sonia Cabrera, Nuria Turcq, Béatrice Prouzet-Mauleon, Valérie Falcone, Mattia Villanueva Garatachea, Alberto Wang, Haiyun Herfs, Michael Mosteiro, Miguel Jänne, Pasi A. Pujol, Jean-Louis Maraver, Antonio Barbacid, Mariano Nadal, Ernest Santamaria, David Ambrogio, Chiara |
Keywords: | Càncer de pulmó Quimioteràpia Lung cancer Chemotherapy |
Issue Date: | 6-Aug-2020 |
Publisher: | American Society for Clinical Investigation Inc. |
Abstract: | Platinum-based chemotherapy in combination with immune-checkpoint inhibitors is the current standard of care for patients with advanced lung adenocarcinoma (LUAD). However, tumor progression evolves in most cases. Therefore, predictive bioma ricers are needed for better patient stratification and for the identification of new therapeutic strategies, including enhancing the efficacy of chemotoxic agents. Here, we hypothesized that discoidin domain receptor 1 (DDR1) may be both a predictive factor for chemoresistance in patients with LUAD and a potential target positively selected in resistant cells. By using biopsies from patients with LUAD, KRAS-mutant LUAD cell lines, and in vivo genetically engineered KRAS-driven mouse models, we evaluated the role of DDR1 in the context of chemotherapy treatment. We found that DORT is upregulated during chemotherapy both in vitro and in viva. Moreover, analysis of a cohort of patients with LUAD suggested that high DOR1 levels in pretreatment biopsies correlated with poor response to chemotherapy. Additionally, we showed that combining DORI inhibition with chemotherapy prompted a synergistic therapeutic effect and enhanced cell death of KRAS-mutant tumors in vivo. Collectively, this study suggests a potential role for DDR1 as both a predictive and prognostic biomarker, potentially improving the chemotherapy response of patients with LUAD. |
Note: | Reproducció del document publicat a: https://doi.org/10.1172/jci.insight.137869 |
It is part of: | JcCIInsight, 2020, vol. 5, num. 15 |
URI: | http://hdl.handle.net/2445/173471 |
Related resource: | https://doi.org/10.1172/jci.insight.137869 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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NokinMJ.pdf | 24.04 MB | Adobe PDF | View/Open |
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