100 (PB090) - Synergy of the novel dual TTK/PLK1 mitotic checkpoint inhibitor (MCI) BAL0891 with paclitaxel and carboplatin in mouse models of human cancer

Abstract

Background: BAL0891 is a first-in-class dual inhibitor of threonine tyrosine kinase (TTK) and polo-like kinase 1 (PLK1). Both kinases collaborate in activating the spindle assembly checkpoint (SAC) to regulate chromosome alignment and segregation before the cell can exit mitosis. In vitro treatment of tumor cells with BAL0891 leads to rapid SAC disruption and accumulation of cells with aberrant chromosome numbers. The resultant genetic instability suggests a potential for combination effects with approved cytotoxic therapies, such as paclitaxel and carboplatin.