Identification of CDK10 as an Important Determinant of Resistance to Endocrine Therapy for Breast Cancer

摘要: Therapies that target estrogen signaling have transformed the treatment of breast cancer. However, effectiveness these agents is limited by development resistance. Here, an RNAi screen was used to identify modifiers tamoxifen sensitivity. We demonstrate CDK10 important determinant resistance endocrine therapies and show silencing increases ETS2-driven transcription c-RAF, resulting in MAPK pathway activation loss tumor cell reliance upon signaling. Patients with ER alpha-positive tumors express low levels relapse early on tamoxifen, demonstrating clinical significance observations. The association methylation promoter suggests a mechanism which expression reduced tumors.