TY  - JOUR
A1  - Montenegro, Raquel Carvalho
A1  - Clark, Peter G. K.
A1  - Howarth, Alison
A1  - Wan, Xiao
A1  - Ceroni, Alessandro
A1  - Siejka, Paulina
A1  - Nunez-Alonso, Graciela A.
A1  - Monteiro, Octovia
A1  - Rogers, Catherine
A1  - Gamble, Vicki
A1  - Burbano, Rommel
A1  - Brennan, Paul E.
A1  - Tallant, Cynthia
A1  - Ebner, Daniel
A1  - Fedorov, Oleg
A1  - O’Neill, Eric M.
A1  - Knapp, Stefan
A1  - Dixon, Darren
A1  - Müller, Susanne
T1  - BET inhibition as a new strategy for the treatment of gastric cancer
T2  - OncoTarget
N2  - Gastric cancer is one of the most common malignancies and a leading cause of cancer death worldwide. The prognosis of stomach cancer is generally poor as this cancer is not very sensitive to commonly used chemotherapies. Epigenetic modifications play a key role in gastric cancer and contribute to the development and progression of this malignancy. In order to explore new treatment options in this target area we have screened a library of epigenetic inhibitors against gastric cancer cell lines and identified inhibitors for the BET family of bromodomains as potent inhibitors of gastric cancer cell proliferations. Here we show that both the pan-BET inhibitor (+)-JQ1 as well as a newly developed specific isoxazole inhibitor, PNZ5, showed potent inhibition of gastric cancer cell growth. Intriguingly, we found differences in the antiproliferative response between gastric cancer cells tested derived from Brazilian patients as compared to those from Asian patients, the latter being largely resistant to BET inhibition. As BET inhibitors are entering clinical trials these findings provide the first starting point for future therapies targeting gastric cancer.
KW  - epigenetic
KW  - bromodomain
KW  - BET inhibitors
KW  - cytotoxicity
KW  - gastric cancer
Y1  - 2016
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/45339
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-453394
SN  - 1949-2553
N1  - All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
VL  - 7
IS  - 28
SP  - 43997
EP  - 44012
PB  - Impact Journals LLC
CY  - [s. l.]
ER  -