- The RAS-related GTPase RHOB confers resistance to EGFR-tyrosine kinase inhibitors in non-small-cell lung cancer via an AKT-dependent mechanism.
The RAS-related GTPase RHOB confers resistance to EGFR-tyrosine kinase inhibitors in non-small-cell lung cancer via an AKT-dependent mechanism.
EMBO molecular medicine (2016-12-23)
Olivier Calvayrac, Julien Mazières, Sarah Figarol, Claire Marty-Detraves, Isabelle Raymond-Letron, Emilie Bousquet, Magali Farella, Estelle Clermont-Taranchon, Julie Milia, Isabelle Rouquette, Nicolas Guibert, Amélie Lusque, Jacques Cadranel, Nathalie Mathiot, Ariel Savina, Anne Pradines, Gilles Favre
PMID28003335
摘要
Although lung cancer patients harboring EGFR mutations benefit from treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKI), most of them rapidly relapse. RHOB GTPase is a critical player in both lung carcinogenesis and the EGFR signaling pathway; therefore, we hypothesized that it could play a role in the response to EGFR-TKI In a series of samples from EGFR-mutated patients, we found that low RHOB expression correlated with a good response to EGFR-TKI treatment while a poor response correlated with high RHOB expression (15.3 versus 5.6 months of progression-free survival). Moreover, a better response to EGFR-TKI was associated with low RHOB levels in a panel of lung tumor cell lines and in a lung-specific tetracycline-inducible EGFR
材料