Author/Authors :
Sheng، نويسنده , , Qing and Liu، نويسنده , , Xinggang and Fleming، نويسنده , , Eleanor and Yuan، نويسنده , , Karen and Piao، نويسنده , , Huiying and Chen، نويسنده , , Jinyun and Moustafa، نويسنده , , Zeinab and Thomas، نويسنده , , Roman K. and Greulich، نويسنده , , Heidi and Schinzel، نويسنده , , Anna and Zaghlul، نويسنده , , Sara and Batt، نويسنده , , David and Ettenberg، نويسنده , , Seth and Meyerson، نويسنده , , Matthew and Schoeberl، نويسنده , , Birgit and Kung، نويسنده , , Andrew L. and Hahn، نويسنده , , William C. and Drapkin، نويسنده , , Ronny and Livingston، نويسنده , , David M. and Liu، نويسنده , , Joyce F.، نويسنده ,
Abstract :
Summary
n cancer is a leading cause of death from gynecologic malignancies. Treatment for advanced-stage disease remains limited and, to date, targeted therapies have been incompletely explored. By systematically suppressing each human tyrosine kinase in ovarian cancer cell lines by RNAi, we found that an autocrine signal-transducing loop involving NRG1 and activated ErbB3 operates in a subset of primary ovarian cancers and ovarian cancer cell lines. Perturbation of this circuit with ErbB3-directed RNAi decreased cell growth in three-dimensional culture and resulted in decreased disease progression and prolonged survival in a xenograft mouse model of ovarian cancer. Furthermore, a monoclonal ErbB3-directed antibody (MM-121) also significantly inhibited tumor growth in vivo. These findings identify ErbB3 as a potential therapeutic target in ovarian cancer.
