Wayne Blosser

TL;DR: Analysis of circulating tumor DNA revealed emergence of RET G810R, G810S, and G810C mutations in the RET solvent front before the emergence of clinical resistance, which represents the first described recurrent mechanism of resistance to selective RET inhibition with selpercatinib.

TL;DR: The characterization of a novel CHK1 inhibitor, LY2606368, which as a single agent causes double-stranded DNA breakage while simultaneously removing the protection of the DNA damage checkpoints is described, suggesting replication catastrophe as the mechanism of DNA damage.

TL;DR: Genetic suppression screens identified enforcers of the spindle assembly checkpoint (SAC) as essential for LY3295668 cytotoxicity in Rb-deficient cancers and suggest a model in which a primed SAC creates a unique dependency on AurA kinase for mitotic exit and survival.

TL;DR: LY2603618 is a potent and selective small molecule inhibitor of Chk1 protein kinase activity in vitro and the first selective Chk 1 inhibitor to enter clinical cancer trials.

TL;DR: Pediatric sarcoma cell lines were highly sensitive to prexasertib treatment in vitro, resulting in activation of the DNA damage response, and concurrent administration with chemotherapy was sufficient to overcome innate resistance or prevent acquired resistance toPrex asertib in preclinical models of neuroblastoma, osteosarcoma, and Ewing sarcomA, or alveolar rhabdomyosar coma.