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Identification of CDK10 as an important determinant of resistance to endocrine therapy for breast cancer.

Abstract：

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

journal_name

Cancer Cell

journal_title

Cancer cell

authors

Iorns E,Turner NC,Elliott R,Syed N,Garrone O,Gasco M,Tutt AN,Crook T,Lord CJ,Ashworth A

doi

10.1016/j.ccr.2008.01.001

subject

Has Abstract

pub_date

2008-02-01 00:00:00

pages

91-104

issue

2

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(08)00004-4

journal_volume

13

pub_type

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