1. High Proliferation Rate and a Compromised Spindle Assembly Checkpoint Confers Sensitivity to the MPS1 Inhibitor BOS172722 in Triple-Negative Breast Cancers
- Author
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Simon J, Anderhub, Grace Wing-Yan, Mak, Mark D, Gurden, Amir, Faisal, Konstantinos, Drosopoulos, Katie, Walsh, Hannah L, Woodward, Paolo, Innocenti, Isaac M, Westwood, Sébastien, Naud, Angela, Hayes, Efthymia, Theofani, Simone, Filosto, Harry, Saville, Rosemary, Burke, Rob L M, van Montfort, Florence I, Raynaud, Julian, Blagg, Swen, Hoelder, Suzanne A, Eccles, and Spiros, Linardopoulos more...
- Subjects
Paclitaxel ,Cell Cycle ,PTEN Phosphohydrolase ,Biological Availability ,Cell Cycle Proteins ,Drug Synergism ,Triple Negative Breast Neoplasms ,Cell Cycle Checkpoints ,Spindle Apparatus ,Protein Serine-Threonine Kinases ,Protein-Tyrosine Kinases ,Triazoles ,Mice ,Pyrimidines ,Cell Line, Tumor ,Chromosome Segregation ,Animals ,Chromosomes, Human ,Humans ,Cell Proliferation - Abstract
BOS172722 (CCT289346) is a highly potent, selective, and orally bioavailable inhibitor of spindle assembly checkpoint kinase MPS1. BOS172722 treatment alone induces significant sensitization to death, particularly in highly proliferative triple-negative breast cancer (TNBC) cell lines with compromised spindle assembly checkpoint activity. BOS172722 synergizes with paclitaxel to induce gross chromosomal segregation defects caused by MPS1 inhibitor-mediated abrogation of the mitotic delay induced by paclitaxel treatment. In more...
- Published
- 2018