de Graaff, Marieke Ade Rooij, Marije A Jvan den Akker, Brendy E W MGelderblom, HansChibon, FrédericCoindre, Jean-MichelMarino-Enriquez, AdrianFletcher, JonathanCleton-Jansen, Anne-MarieBovée, Judith V M G2017-06-152016de Graaff, Marieke A, Marije A J de Rooij, Brendy E W M van den Akker, Hans Gelderblom, Fréderic Chibon, Jean-Michel Coindre, Adrian Marino-Enriquez, Jonathan A Fletcher, Anne-Marie Cleton-Jansen, and Judith V M G Bovée. 2016. “Inhibition of Bcl-2 family members sensitises soft tissue leiomyosarcomas to chemotherapy.” British Journal of Cancer 114 (11): 1219-1226. doi:10.1038/bjc.2016.117. http://dx.doi.org/10.1038/bjc.2016.117.http://nrs.harvard.edu/urn-3:HUL.InstRepos:33029833Background: Leiomyosarcoma is an aggressive soft tissue sarcoma with a 5-year survival rate of 15 to 60%. Treatment options for inoperable or metastatic patients are limited owing to frequent resistance of tumours to chemotherapy and radiation. In this study, we hypothesised that antiapoptotic Bcl-2 family proteins might contribute to leiomyosarcoma chemoresistance and therefore inhibition of Bcl-2 family proteins might sensitise leiomyosarcomas to conventional chemotherapy. Methods: Expression of the Bcl-2 family proteins Bcl-xL, Bcl-w and Bcl-2 was investigated using immunohistochemistry on a tissue microarray containing 43 leiomyosarcomas. Furthermore, we investigated whether ABT-737, a potent BH3 mimetic, sensitises leiomyosarcoma cells to doxorubicin treatment in vitro. Results: Seventy-seven per cent, 84% and 42% of leiomyosarcomas demonstrated high expression of Bcl-2, Bcl-xL and Bcl-w, respectively. Single-agent treatment with ABT-737 resulted in a minor reduction of cell viability. However, combination treatment of ABT-737 and doxorubicin revealed synergism in all four cell lines, by inducing apoptosis. Conclusions: In conclusion, Bcl-2 family proteins contribute to soft tissue leiomyosarcoma chemoresistance. Antiapoptotic proteins are highly expressed in leiomyosarcoma of soft tissue, and inhibition of these proteins using a BH3 mimetic increases leiomyosarcoma sensitivity to doxorubicin.en-USsarcomaleiomyosarcomasoft tissue tumourapoptosisBcl-2Bcl-xLBcl-wABT-737chemoresistanceJournal Article2017-06-1510.1038/bjc.2016.117