Academic Journal
Heterogeneous Mechanisms of Primary and Acquired Resistance to Third-Generation EGFR Inhibitors
| العنوان: | Heterogeneous Mechanisms of Primary and Acquired Resistance to Third-Generation EGFR Inhibitors |
|---|---|
| المؤلفون: | Ortiz-Cuaran, Sandra, Scheffler, Matthias, Plenker, Dennis, Dahmen, Ilona, Scheel, Andreas H., Fernandez-Cuesta, Lynnette, Meder, Lydia, Lovly, Christine M., Persigehl, Thorsten, Merkelbach-Bruse, Sabine, Bos, Marc, Michels, Sebastian, Fischer, Rieke, Albus, Kerstin, Koenig, Katharina, Schildhaus, Hans-Ulrich, Fassunke, Jana, Ihle, Michaela A., PasternackO, Helen, Heydt, Carina, Becker, Christian, Altmueller, Janine, Ji, Hongbin, Mueller, Christian, Florin, Alexandra, Heuckmann, Johannes M., Nuernberg, Peter, Ansen, Sascha, Heukamp, Lukas C., Berg, Johannes, Pao, William, Peifer, Martin, Buettner, Reinhard, Wolfe, Juergen, Thomas, Roman K., Sos, Martin L. |
| بيانات النشر: | AMER ASSOC CANCER RESEARCH |
| سنة النشر: | 2016 |
| المجموعة: | Cologne University: KUPS |
| مصطلحات موضوعية: | ddc:no |
| الوصف: | Purpose: To identify novel mechanisms of resistance to third-generation EGFR inhibitors in patients with lung adenocarcinoma that progressed under therapy with either AZD9291 or rociletinib (CO-1686). Experimental Design: We analyzed tumor biopsies from seven patients obtained before, during, and/or after treatment with AZD9291 or rociletinib (CO-1686). Targeted sequencing and FISH analyses were performed, and the relevance of candidate genes was functionally assessed in in vitro models. Results: We found recurrent amplification of either MET or ERBB2 in tumors that were resistant or developed resistance to third-generation EGFR inhibitors and show that ERBB2 and MET activation can confer resistance to these compounds. Furthermore, we identified a KRAS(G12S) mutation in a patient with acquired resistance to AZD9291 as a potential driver of acquired resistance. Finally, we show that dual inhibition of EGFR/MEK might be a viable strategy to overcome resistance in EGFR-mutant cells expressing mutant KRAS. Conclusions: Our data suggest that heterogeneous mechanisms of resistance can drive primary and acquired resistance to third-generation EGFR inhibitors and provide a rationale for potential combination strategies. (C) 2016 AACR. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | Ortiz-Cuaran, Sandra, Scheffler, Matthias orcid:0000-0002-9031-1368 , Plenker, Dennis, Dahmen, Ilona, Scheel, Andreas H., Fernandez-Cuesta, Lynnette orcid:0000-0002-0724-6703 , Meder, Lydia orcid:0000-0002-9547-5812 , Lovly, Christine M., Persigehl, Thorsten, Merkelbach-Bruse, Sabine, Bos, Marc, Michels, Sebastian, Fischer, Rieke, Albus, Kerstin, Koenig, Katharina, Schildhaus, Hans-Ulrich, Fassunke, Jana, Ihle, Michaela A., PasternackO, Helen, Heydt, Carina, Becker, Christian, Altmueller, Janine, Ji, Hongbin, Mueller, Christian, Florin, Alexandra, Heuckmann, Johannes M., Nuernberg, Peter, Ansen, Sascha, Heukamp, Lukas C., Berg, Johannes, Pao, William, Peifer, Martin orcid:0000-0002-5243-5503 , Buettner, Reinhard, Wolfe, Juergen, Thomas, Roman K. and Sos, Martin L. (2016). Heterogeneous Mechanisms of Primary and Acquired Resistance to Third-Generation EGFR Inhibitors. Clin. Cancer Res., 22 (19). S. 4837 - 4848. PHILADELPHIA: AMER ASSOC CANCER RESEARCH. ISSN 1557-3265 |
| الاتاحة: | https://kups.ub.uni-koeln.de/26137/ |
| رقم الانضمام: | edsbas.F412C88E |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |