EZH2 inhibition sensitizes BRG1 and EGFR mutant lung tumors to TopoII inhibitors
نویسندگان
چکیده
Christine M. Fillmore1,2,3, Chunxiao Xu4,5, Pooja T. Desai1, Joanne M. Berry1, Samuel P. Rowbotham1,2,3, Yi-Jang Lin2, Haikuo Zhang4,5, Victor E. Marquez6, Peter S. Hammerman4, Kwok-Kin Wong4,5, and Carla F. Kim1,2,3,7 1 Stem Cell Program, Boston Children’s Hospital, Boston MA 02115 USA 2 Department of Genetics, Harvard Medical School, Boston, MA 02115 USA 3 Harvard Stem Cell Institute, Cambridge, MA 02138 USA 4 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115 USA 5 Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston MA 02115 USA
منابع مشابه
Inhibition of Hsp90 down-regulates mutant epidermal growth factor receptor (EGFR) expression and sensitizes EGFR mutant tumors to paclitaxel.
Mutations in the kinase domain of the epidermal growth factor receptor (EGFR) are found in a subset of patients with lung cancer and correlate with response to EGFR tyrosine kinase inhibitors (TKI). Resistance to these agents invariably develops, and current treatment strategies have limited efficacy in this setting. Hsp90 inhibitors, such as 17-allylamino-17-demethoxygeldanamycin (17-AAG), ind...
متن کاملInduction of BIM Is Essential for Apoptosis Triggered by EGFR Kinase Inhibitors in Mutant EGFR-Dependent Lung Adenocarcinomas
BACKGROUND Mutations in the epidermal growth factor receptor (EGFR) gene are associated with increased sensitivity of lung cancers to kinase inhibitors like erlotinib. Mechanisms of cell death that occur after kinase inhibition in these oncogene-dependent tumors have not been well delineated. We sought to improve understanding of this process in order to provide insight into mechanisms of sensi...
متن کاملInhibition of EZH2 by chemo- and radiotherapy agents and small molecule inhibitors induces cell death in castration-resistant prostate cancer
Androgen deprivation therapy is the mainstay of treatment of advanced prostate cancer (PCa). However, a significant portion of patients experience disease relapse and tumors ultimately evolve into castration resistant prostate cancer (CRPC), for which there is no cure in the clinic. The Polycomb protein enhancer of zeste homolog 2 (EZH2) is frequently overexpressed in CRPC. It is unclear whethe...
متن کاملHER2 Amplifi cation: A Potential Mechanism of Acquired Resistance to EGFR Inhibition in EGFR -Mutant Lung Cancers That Lack the Second-Site EGFR
EGF receptor (EGFR) –mutant lung cancers eventually become resistant to treatment with EGFR tyrosine kinase inhibitors (TKI). The combination of EGFR-TKI afatinib and anti-EGFR antibody cetuximab can overcome acquired resistance in mouse models and human patients. Because afatinib is also a potent HER2 inhibitor, we investigated the role of HER2 in EGFR-mutant tumor cells. We show in vitro and ...
متن کاملInhibition of Shp2 suppresses mutant EGFR-induced lung tumors in transgenic mouse model of lung adenocarcinoma
Epidermal growth factor receptor (EGFR) mutants drive lung tumorigenesis and are targeted for therapy. However, resistance to EGFR inhibitors has been observed, in which the mutant EGFR remains active. Thus, it is important to uncover mediators of EGFR mutant-driven lung tumors to develop new treatment strategies. The protein tyrosine phosphatase (PTP) Shp2 mediates EGF signaling. Nevertheless,...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 520 شماره
صفحات -
تاریخ انتشار 2015