Kinase-Mediated Regulation of 40S Ribosome Assembly in Human Breast Cancer
Abstract
There are several clinical applications of our Breakthrough studies. First, the proposed studies will validate the CK1d-to-ribosome assembly pathway as an exploitable vulnerability for TNBC, which would support efforts for fast-tracking suchCK1d-selective agents into the breast oncology clinic. Second, if our studies prove successful (as we fully expect) they will support new anti-cancer drug campaigns that seek to disable the functions of other assembly factors that are necessary for the proper assembly of ribosomes with ~200 assembly factors that one could target this is a rich arena for developing a whole new cast of cancer therapeutics, for TNBC, HER2+ and luminal B breast cancers and likely many other tumor types. Third, our studies will define the mechanism by which CK1d inhibitors block TNBC cell growth and survival. This will allow for the identification of biomarkers, which are needed to show that these drugs are indeed on target in the tumors of patients treated with these agents, for example by evaluating effects of these drugs on the quantity of ribosomes in tumor cells (which can be quantified by staining tumor sections with a dye that detects RNA). Finally, our proposed studies may reveal potential mechanisms for the development of resistance to CK1d inhibitors and, using FDA approved drugs, they will test new.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2019
- Accession Number
- AD1095170
Entities
People
- Katrin Karbstein