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Breast cancer is often treated with hormonal therapy, but resistance to treatment is common. This implies that current breast cancer treatment regimes do not suffice in efficiently eradicating the tumor. Here, we intent to develop a novel type of breast cancer treatment that is aimed at blocking not the hormonal receptor itself but other proteins that are essential for hormone receptor function. We found that the specific proteins involved in ubiquitin/proteasome-mediated protein degradation are required for Estrogen Receptor expression, activity and Estrogen Receptor-mediated cell proliferation. Therefore, we aim to identify novel inhibitors that selectively inhibit these specific proteins in this pathway.
The ubiquitin system holds many potential therapeutic targets but due to the lack of appropriate assay reagents it remains largely unexplored for drug development. If successful, this project will be one of the first and few proven examples of effective drug discovery in the ubiquitin system.
Project title: A new angle to breast cancer drug development
Principal Investigator: Dr. Wilbert Zwart
Partners: UbiQ, Pivot Park Screening Centre, NKI
Budget: 890 kEUR
Start: 1 December 2012
End: 31 May 2014