Work

105P Discovery of potent and selective PKMYT1 inhibitors

Year: 2026

Type: article

Abstract: The cell-cycle regulator cyclin E1 is frequently overexpressed in ovarian, endometrial, and colorectal cancers due to CCNE1 gene amplification, reduced degradation (via FBXW7 mut/del), or increased gene transcription. High levels of cyclin E1 dysregulate the G1/S checkpoint, increase replication stress, and amplify dependence on the G2/M checkpoint to ensure proper DNA damage repair before mitosis. Additionally, high cyclin E1 levels are associated with poor prognosis and poor response to therapy, highlighting the need for improved treatments for cyclin E1-high cancers.

Source: ESMO Open

DOI: 10.1016/j.esmoop.2026.106247