| Added by | amaraver |
|---|---|
| Group name | EquipeAM |
| Item Type | Journal Article |
| Title | The RAS-related GTPase RHOB confers resistance to EGFR-tyrosine kinase inhibitors in non-small-cell lung cancer via an AKT-dependent mechanism |
| Creator | Calvayrac et al. |
| Author | Olivier Calvayrac |
| Author | Julien Mazières |
| Author | Sarah Figarol |
| Author | Claire Marty-Detraves |
| Author | Isabelle Raymond-Letron |
| Author | Emilie Bousquet |
| Author | Magali Farella |
| Author | Estelle Clermont-Taranchon |
| Author | Julie Milia |
| Author | Isabelle Rouquette |
| Author | Nicolas Guibert |
| Author | Jacques Cadranel |
| Author | Nathalie Mathiot |
| Author | Ariel Savina |
| Author | Anne Pradines |
| Author | Gilles Favre |
| Abstract | 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 EGFRL858R transgenic mouse model. High RHOB expression was also found to prevent erlotinib-induced AKT inhibition in vitro and in vivo Furthermore, a combination of the new-generation AKT inhibitor G594 with erlotinib induced tumor cell death in vitro and tumor regression in vivo in RHOB-positive cells. Our results support a role for RHOB/AKT signaling in the resistance to EGFR-TKI and propose RHOB as a potential predictor of patient response to EGFR-TKI treatment. |
| Publication | EMBO molecular medicine |
| Volume | 9 |
| Issue | 2 |
| Pages | 238-250 |
| Date | 02 2017 |
| Journal Abbr | EMBO Mol Med |
| Language | eng |
| DOI | 10.15252/emmm.201606646 |
| ISSN | 1757-4684 |
| Library Catalog | PubMed |
| Extra | PMID: 28003335 PMCID: PMC5286377 |
| Tags | AKT, Animals, Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Drug Resistance, EGFR, Enzyme Inhibitors, Humans, Mice, Mice, Transgenic, original, Protein-Tyrosine Kinases, Proto-Oncogene Proteins c-akt, Receptor, Epidermal Growth Factor, RhoB, rhoB GTP-Binding Protein, TKI |
| Date Added | 2018/11/15 - 17:04:24 |
| Date Modified | 2019/05/16 - 10:59:06 |
| Notes and Attachments | Full Text (Attachment) PubMed entry (Attachment) |
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