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Gene Symbol CHEK1
Synonyms CHK1 | OZEMA21
Gene Description CHEK1, checkpoint kinase 1, is a serine/threonine kinase activated in response to DNA damage that is responsible for mediating checkpoint signaling from ATM and ATR (PMID: 23613359, PMID: 12781359). Overexpression of Chek1 has been observed in several tumor types, including gastric cancer, small cell lung cancer, T-cell leukemia (PMID: 25132270, PMID: 26867682, PMID: 28490518), and breast cancer (PMID: 31933717).
NCBI Gene ID Chromosome Map Location Canonical Transcript Gene Role
1111 11 11q24.2 NM_001114121 Unknown

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
CHEK1 positive lung non-small cell carcinoma predicted - sensitive Prexasertib Preclinical - Cell line xenograft Actionable In a preclinical study, Prexasertib (LY2606368) increased apoptosis of non-small cell lung cancer (NSCLC) cells in culture, and inhibited Chek1 phosphorylation, induced DNA damage, and reduced tumor growth in a NSCLC cell line xenograft model (PMID: 26141948). 26141948
CHEK1 positive head and neck squamous cell carcinoma sensitive CCT244747 + Radiotherapy Preclinical - Cell culture Actionable In a preclinical study, CCT244747 inhibited Chek1 activation, resulted in sensitizing head and neck squamous cell carcinoma cell lines to radiation treatment in culture (PMID: 27422809). 27422809
CHEK1 positive head and neck squamous cell carcinoma sensitive CCT244747 + Paclitaxel + Radiotherapy Preclinical - Cell line xenograft Actionable In a preclinical study, CCT244747, Taxol (paclitaxel), and radiation triple therapy synergistically inhibited Chek1 activation, and resulted in growth inhibition of head and neck squamous cell carcinoma cell lines in culture and in cell line xenograft models (PMID: 27422809). 27422809
CHEK1 positive colon cancer predicted - sensitive CCT244747 + Gemcitabine Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of CCT244747 and Gemzar (gemcitabine) slowed tumor growth to a greater degree than treatment with either agent alone and decreased Chek1 phosphorylation in colon cancer cell line xenograft models (PMID: 22929806). 22929806
CHEK1 inact mut prostate cancer sensitive Olaparib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) treatment significantly improved median imaging-based progression-free survival (5.8 vs 3.5 mo, HR 0.49, p<0.001) compared to control in patients with metastatic castration-resistant prostate cancer who progressed on hormone therapy and harbored deleterious or suspected deleterious mutations in homologous recombination repair genes, including CHEK1 (PMID: 32343890; NCT02987543). detail... detail... 32343890
CHEK1 inact mut prostate cancer sensitive Olaparib Guideline Actionable Lynparza (olaparib) is included in guidelines as second-line therapy post androgen receptor-directed therapy for patients with metastatic castration-resistant prostate cancer harboring pathogenic mutations in CHEK1 (NCCN.org). detail...
CHEK1 over exp lung small cell carcinoma sensitive PF-00477736 Preclinical - Cell line xenograft Actionable In a preclinical study, small cell lung cancer cell lines, which expressed high levels of CHEK1, demonstrated sensitivity to PF-00477736 treatment, resulting in decreased viability in culture and reduced tumor growth in xenograft models (PMID: 29138515). 29138515
CHEK1 over exp lung small cell carcinoma sensitive Berzosertib Preclinical - Cell line xenograft Actionable In a preclinical study, small cell lung cancer cell lines, which expressed high levels of CHEK1, demonstrated sensitivity to Berzosertib (VX-970) treatment, resulting in decreased viability in culture and reduced tumor growth in xenograft models (PMID: 29138515). 29138515