Ras–MEK Signaling Mediates a Critical Chk1-Dependent DNA Damage Response in Cancer Cells

Abstract excerpt

Abstract Cancer cell line profiling to identify previously unrecognized kinase dependencies revealed a novel nonmutational dependency on the DNA damage response checkpoint kinase Chk1. Although Chk1 is a promising therapeutic target in p53-deficient cancers, we found that Ras–MEK signaling engages Chk1 in a subset of osteosarcoma, ovarian, and breast cancer cells to enable their survival upon DNA damage,...