CHEK1
Overview
CHEK1 (Checkpoint Kinase 1) is a central regulator of the DNA damage response (DDR) and replication stress checkpoint. CHEK1 inhibition is synthetically lethal with FBXO7 loss in colorectal cancer, providing a therapeutic rationale for CHEK1 inhibitor use in genomically selected CRC patients.
Alterations observed in the corpus
- Synthetic lethal interactor of FBXO7; CHEK1 inhibition via siRNA or prexasertib preferentially kills FBXO7-deficient CRC cells; central to replication stress response and DDR checkpoint control PMID:36334560
- CHEK1 identified in functional genomics screen as relevant to DNA damage response in ARID1A-mutant ovarian cancer cells treated with BET bromodomain inhibitors PMID:22037554
- Upregulated in basal-like IntClust 10 as part of a chromosome 5q deletion-associated trans-acting mitotic network in the METABRIC breast cancer cohort (2,000 tumors) PMID:22522925
Cancer types (linked)
- CRC: CHEK1 inhibition synthetically lethal in FBXO7-deleted tumors PMID:36334560
Co-occurrence and mutual exclusivity
- CHEK1 inhibition exploits FBXO7 copy number loss in CRC PMID:36334560
Therapeutic relevance
- Prexasertib (CHEK1 inhibitor) preferentially kills FBXO7-deficient CRC cells in preclinical models PMID:36334560
Open questions
- Clinical validation of prexasertib in FBXO7-deleted CRC patients is needed.
Sources
This page was processed by crosslinker on 2026-05-06. - PMID:22037554
This page was processed by wiki-cli on 2026-05-06. - PMID:22522925
This page was processed by wiki-cli on 2026-05-06.