Sign up & Download
Sign in

Parallel RNAi and compound screens identify the PDK1 pathway as a target for tamoxifen sensitization.

by Elizabeth Iorns, Christopher J Lord, Alan Ashworth
The Biochemical journal ()

Abstract

Tamoxifen is the most commonly used drug to treat breast cancer and acts by blocking ERalpha (oestrogen receptor alpha) signalling. Although highly effective, its usefulness is limited by the development of resistance. Given this, strategies that limit resistance by sensitizing cells to tamoxifen may be of use in the clinic. To gain insight into how this might be achieved, we used chemical and genetic screens to identify targets and small-molecule inhibitors that cause tamoxifen sensitization. A high-throughput genetic screen, using an RNA interference library targeting 779 kinases and related proteins, identified the PDK1 (phosphoinositide-dependent kinase 1) signalling pathway as a strong determinant of sensitivity to multiple ERalpha antagonists, including tamoxifen. A chemical screen using existing drugs and known kinase inhibitors also identified inhibitors of the PDK1 pathway, including triciribine and tetrandrine. Aside from identifying novel agents and targets for tamoxifen sensitization, this approach also provides evidence that performing chemical and genetic screens in parallel may be useful.

Cite this document (BETA)

Authors on Mendeley

Readership Statistics

17 Readers on Mendeley
by Discipline
 
 
by Academic Status
 
47% Ph.D. Student
 
12% Post Doc
 
12% Assistant Professor
by Country
 
12% United States
 
6% Netherlands
 
6% Germany

Sign up today - FREE

Mendeley saves you time finding and organizing research. Learn more

  • All your research in one place
  • Add and import papers easily
  • Access it anywhere, anytime

Start using Mendeley in seconds!

Already have an account? Sign in