MTOR inhibition overcomes primary and acquired resistance to Wee1 inhibition by augmenting replication stress in epithelial ovarian cancers.

ABSTRACT: Epithelial ovarian cancer is characterized by universal TP53 mutations, which result in G1/S checkpoint deficiencies. Therefore, it is hypothesized that the abrogation of the G2/M checkpoint with Wee1 inhibitor might preferentially sensitize TP53-defective ovarian cancer cells. Given the extremely high molecular diversity in ovarian cancer, one approach to improving the clinical efficacy is to identify drug combinations that either broaden the applicable spectrum or circumvent resistance. Here, through a high-throughput unbiased proteomic profiling (RPPA), we found the complementary activated mTOR pathway contributes greatly to Wee1 inhibitor resistance. A combination of Wee1 and mTOR inhibits synergistically inhibiting tumor growth in ovarian cancer cell lines and patient-derived xenograf

SUBMITTER: Li F 

PROVIDER: S-EPMC7136919 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature