^
    Contact us  to learn more about
    our Premium Content:  News alerts, weekly reports and conference planners
    GENE:

    CHEK2 (Checkpoint kinase 2)

    i
    Other names: CHEK2, bA444G7, CDS1, CHK2, HuCds1, PP1425, RAD53, Checkpoint kinase 2
    2d
    Small Molecule Activators of the Mitochondrial Protease ClpP Induce Senescence in Triple-Negative Breast Cancer Cells and Sensitize Cells to the Bcl-2 Inhibitor Venetoclax. (PubMed, Res Sq)
    We report that ONC201 and highly potent second generation ClpP agonists (TR-57, TR-107), promote induction of senescence in triple-negative breast cancer (TNBC) cell lines...By contrast, cells treated with the cell cycle inhibitor and senescence inducer, abemaciclib rapidly regained p-Rb and Myc expression and cell proliferation following washout...Combining a ClpP agonist with a PARP inhibitor (olaparib) produced an additive effect. In summary, we show that ClpP activators stably induce an irreversible senescence in a ClpP-dependent manner that synergizes with venetoclax in TNBC cells.
    Journal • PARP Biomarker • IO biomarker
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CHEK2 (Checkpoint kinase 2) • TP53BP1 (Tumor Protein P53 Binding Protein 1)
    |
    Venclexta (venetoclax) • Lynparza (olaparib) • Verzenio (abemaciclib) • nesuparib (JPI-547) • Modeyso (dordaviprone)
    2d
    Skin cancer risk in hereditary mixed cancer syndromes. (PubMed, Hered Cancer Clin Pract)
    This review consolidates existing evidence and suggests that mixed cancer syndromes, especially LFS, LS, and HBOC but also pathogenic ATM and CHEK2 variants may predispose individuals to skin cancers, warranting tailored screening and preventive measures. On the basis of emerging evidence, we recommend dermatologic evaluation and individualized UV protection strategies for patients with reviewed hereditary cancer syndromes to reduce skin cancer risk and enhance early detection.
    Review • Journal
    |
    CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1)
    3d
    NIRADO: Basket Trial Exploring the Efficacy and Safety of the Combination of Niraparib and Dostarlimab (clinicaltrials.gov)
    P2, N=51, Terminated, Gustave Roussy, Cancer Campus, Grand Paris | Trial completion date: Dec 2027 --> Feb 2025 | Suspended --> Terminated; Abandon of the partner, GSK
    Trial completion date • Trial termination • Pan tumor • Platinum sensitive
    |
    HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ARID1A (AT-rich interaction domain 1A) • PBRM1 (Polybromo 1) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • ARID2 (AT-Rich Interaction Domain 2) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • DRD (DNA Repair Deficiency)
    |
    HER-2 positive • HER-2 amplification • DDR • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • BARD1 mutation
    |
    Zejula (niraparib) • Jemperli (dostarlimab-gxly)
    4d
    ARIANES: Efficacy and Safety of the Combination of Rucaparib (PARP Inhibitor) and Atezolizumab (Anti-PD-L1 Antibody) in Patients With DNA Repair-deficient or Platinum-sensitive Solid Tumors (clinicaltrials.gov)
    P2, N=130, Terminated, Gustave Roussy, Cancer Campus, Grand Paris | Suspended --> Terminated; Bankruptcy of partner: Clovis
    Trial termination • Pan tumor • Platinum sensitive
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • IL2 (Interleukin 2) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • DRD (DNA Repair Deficiency)
    |
    DDR • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • BARD1 mutation
    |
    Tecentriq (atezolizumab) • Rubraca (rucaparib)
    4d
    Pediatric Oncology Patients With Germline Pathogenic Variants in Adult-Onset Cancer Predisposition Genes. (PubMed, JCO Precis Oncol)
    These findings contribute to the literature suggesting that, rarely, GPV in aoCPG may contribute to cancer diagnoses in children, raising the question of how tumors in these cases may present differently in children than adults. Increased knowledge about potential childhood cancer risks related to what have historically been considered aoCPG could modify predictive genetic testing recommendations for children and enhance existing cancer screening protocols.
    Journal • Tumor mutational burden
    |
    TMB (Tumor Mutational Burden) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1)
    6d
    Outcomes for ER-positive CHEK2 c.1100delC breast cancer patients compared with breast cancer patients without the variant. (PubMed, Breast)
    In our study, with more recent years of diagnosis and treatment, we found no difference in prognosis, as opposed to previous studies. Further research is needed to validate our findings.
    Journal
    |
    ER (Estrogen receptor) • CHEK2 (Checkpoint kinase 2)
    |
    ER positive
    7d
    Predisposition of an Intronic Duplication in CHEK2 Gene in the Cases of Breast Cancer from Balochistan. (PubMed, Asian Pac J Cancer Prev)
    Our results suggest that the intronic variant identified in breast cancer cases as well as reported previously may act as a cancer marker and causing a splice site disruption or altering the posttranscriptional modification of mRNA encoded by CHEK2 gene.
    Journal • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2)
    |
    CHEK2 mutation
    8d
    Pan-cancer NK cell-related immunotherapy signatures for predicting PD-1 treatment response. (PubMed, Medicine (Baltimore))
    Additionally, therapeutic evaluation of CHEK1 and CHEK2 targets demonstrated potential significance in the communication between B cells, NK cells, and mast cells within the context of ICI therapy. In summary, the NKCIPM model offers a valuable tool for predicting immunotherapy outcomes and informing clinical decision-making, highlighting the potential of NK cell signature genes as therapeutic targets.
    Journal • Pan tumor
    |
    CHEK2 (Checkpoint kinase 2) • CHEK1 (Checkpoint kinase 1) • APOE (Apolipoprotein E)
    9d
    Germline Mutations in DNA Repair Genes in Patients with Pancreatic Neuroendocrine Neoplasms: Diagnostic and Therapeutic Implications. (PubMed, Curr Oncol)
    These findings indicate that germline mutations in DNA repair genes may contribute to the pathogenesis of pNENs, even in patients without a family history. Broader germline testing and population-specific studies are needed to clarify the genetic landscape and clinical implications of these alterations.
    Journal • BRCA Biomarker
    |
    BRCA2 (Breast cancer 2, early onset) • CHEK2 (Checkpoint kinase 2)
    9d
    Germline Mutation Analysis and Real-World Impact in a Selected Cohort of Patients with Non-Small Cell Lung Cancer: INHERITY LC Study. (PubMed, Clin Lung Cancer)
    The INHERITY LC study identified a PGV prevalence of 10.3% in a selected NSCLC cohort, with most variants affecting genes involved in the DNA damage repair (DDR) pathway. The application of specific selection criteria may enhance the yield of germline testing in this setting. Larger confirmatory studies are warranted to demonstrate that germline testing and genetic counseling for NSCLC may have implications for prevention, early detection, and treatment.
    Clinical • Journal • Real-world evidence • BRCA Biomarker
    |
    TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • CHEK2 (Checkpoint kinase 2) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • XRCC2 (X-Ray Repair Cross Complementing 2)
    10d
    Utility of Biparametric MRI (Magnetic Resonance Imaging) as a Screening Tool for Prostate Cancer in a High-Risk Cohort (clinicaltrials.gov)
    P=N/A, N=100, Recruiting, Northwell Health | Trial completion date: Oct 2026 --> Oct 2028 | Trial primary completion date: Oct 2025 --> Oct 2027
    Trial completion date • Trial primary completion date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • HOXB13 (Homeobox B13)
    11d
    AAV Kills Dividing Cells by Depleting PARP1 and Other DNA Damage Response Proteins. (PubMed, bioRxiv)
    This work fills substantial gaps in the understanding of the mechanisms of rAAV toxicity and has important implications for the development of safer rAAV-based human gene therapies. The rAAV genome binds to and depletes PARP1 and other SSBR proteins that are essential for DNA replication, resulting in DNA double stranded breaks, checkpoint activation, and cell death in dividing cells.
    Journal • PARP Biomarker
    |
    CHEK2 (Checkpoint kinase 2) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • TP53BP1 (Tumor Protein P53 Binding Protein 1)