| Autor: |
Wenyue Hu, Rosa L. Frias, Hovhannes J. Gukasyan, Alice T. Shaw, Valeria Fantin, Ryohei Katayama, Nathan V. Lee, Ruth W. Tang, Timothy Affolter, Eugene Lifshits, Ted William Johnson, Divya Bezwada, David P. Kodack, Lars D. Engstrom, Hieu Lam, Sidra Mahmood, Tod Smeal, Luc Friboulet, Rakesh K. Jain, Hui Wang, Melissa West, Dac M. Dinh, Bhushankumar Patel, Qiuhua Li, Konstantinos Tsaparikos, Helen Y. Zou, Justine L. Lam, Sergei Timofeevski, Shinji Yamazaki, Patrick B. Lappin, Justin F. Gainor, Shibing Deng, Jinwei Wang |
| Rok vydání: |
2015 |
| Předmět: |
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| Zdroj: |
Cancer Cell. 28:70-81 |
| ISSN: |
1535-6108 |
| Popis: |
SummaryWe report the preclinical evaluation of PF-06463922, a potent and brain-penetrant ALK/ROS1 inhibitor. Compared with other clinically available ALK inhibitors, PF-06463922 displayed superior potency against all known clinically acquired ALK mutations, including the highly resistant G1202R mutant. Furthermore, PF-06463922 treatment led to regression of EML4-ALK-driven brain metastases, leading to prolonged mouse survival, in a superior manner. Finally, PF-06463922 demonstrated high selectivity and safety margins in a variety of preclinical studies. These results suggest that PF-06463922 will be highly effective for the treatment of patients with ALK-driven lung cancers, including those who relapsed on clinically available ALK inhibitors because of secondary ALK kinase domain mutations and/or brain metastases. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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