التفاصيل البيبلوغرافية
العنوان: |
Data from Preclinical Characterization of BET Family Bromodomain Inhibitor ABBV-075 Suggests Combination Therapeutic Strategies |
المؤلفون: |
Yu Shen, Warren M. Kati, Keith F. McDaniel, Saul H. Rosenberg, Steven W. Elmore, Guowei Fang, Fred Kohlhapp, Xin Lu, Tamar Uziel, Lisa Hasvold, Dachun Liu, John K. Pratt, Steve Fidanze, Le Wang, George S. Sheppard, Cherrie K. Donawho, Denise Wilcox, Xiaoli Huang, Scott E. Warder, Emily J. Faivre, Lloyd T. Lam, Leiming Li, Daniel H. Albert, Xiaoyu Lin, Mai H. Bui |
بيانات النشر: |
American Association for Cancer Research (AACR), 2023. |
سنة النشر: |
2023 |
الوصف: |
ABBV-075 is a potent and selective BET family bromodomain inhibitor that recently entered phase I clinical trials. Comprehensive preclinical characterization of ABBV-075 demonstrated broad activity across cell lines and tumor models, representing a variety of hematologic malignancies and solid tumor indications. In most cancer cell lines derived from solid tumors, ABBV-075 triggers prominent G1 cell-cycle arrest without extensive apoptosis. In this study, we show that ABBV-075 efficiently triggers apoptosis in acute myeloid leukemia (AML), non-Hodgkin lymphoma, and multiple myeloma cells. Apoptosis induced by ABBV-075 was mediated in part by modulation of the intrinsic apoptotic pathway, exhibiting synergy with the BCL-2 inhibitor venetoclax in preclinical models of AML. In germinal center diffuse large B-cell lymphoma, BCL-2 levels or venetoclax sensitivity predicted the apoptotic response to ABBV-075 treatment. In vivo combination studies uncovered surprising benefits of low doses of ABBV-075 coupled with bortezomib and azacitidine treatment, despite the lack of in vitro synergy between ABBV-075 and these agents. The in vitro/in vivo activities of ABBV-075 described here may serve as a useful reference to guide the development of ABBV-075 and other BET family inhibitors for cancer therapy. Cancer Res; 77(11); 2976–89. ©2017 AACR. |
URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=doi_________::ad920b8eb354003b6c1ac04c4521a267 https://doi.org/10.1158/0008-5472.c.6509072.v1 |
حقوق: |
OPEN |
رقم الأكسشن: |
edsair.doi...........ad920b8eb354003b6c1ac04c4521a267 |
قاعدة البيانات: |
OpenAIRE |