IDENTIFICATION OF SELECTIVE INHIBITORS OF THE SPINDLE ASSEMBLY CHECKPOINT KINASE TTK (MPS1) FOR TREATMENT OF TRIPLE NEGATIVE BREAST CANCER

The protein kinase TTK (commonly referred to as Mps1) is a component of the Spindle Assembly Checkpoint (SAC), a surveillance mechanism that ensures the fidelity of chromosome segregation. Defects in SAC functioning can lead to chromosome segregation errors, resulting in an abnormal number of chromosomes, or ‘aneuploidy’. Aneuploidy is a common feature of solid human tumors and a predictor of poor prognosis in breast, lung, brain and colorectal cancer. TTK mRNA levels are elevated in several cancers, in particular in triple negative breast cancer (TNBC), the most aggressive type of breast cancer.