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    GENE:

    CHEK2 (Checkpoint kinase 2)

    i
    Other names: CHEK2, bA444G7, CDS1, CHK2, HuCds1, PP1425, RAD53, Checkpoint kinase 2
    3ms
    Differences in Cascade Genetic Testing Among Families With Hereditary Cancer Risk. (PubMed, JAMA Netw Open)
    In this retrospective cross-sectional study, cascade testing was underused, especially among specific demographic groups, with clinical and cultural factors appearing to play a larger role than financial barriers. These findings may guide efforts to address barriers preventing wider uptake of cascade testing and improve cancer prevention efforts, particularly among racial and ethnic minority groups.
    Retrospective data • Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • CHEK2 (Checkpoint kinase 2) • EPCAM (Epithelial cell adhesion molecule)
    3ms
    Hepatitis B virus X protein induces E6-associated protein-mediated proteasomal degradation of p53 phosphorylated at Ser-15. (PubMed, J Gen Virol)
    E6AP-mediated p53 degradation was severely impaired in the presence of the ATM inhibitor KU-55933, indicating that HBx-induced p53 phosphorylation plays a critical role in this process. Additionally, E6AP could target p53 phosphorylated by DNA-damaging agents like etoposide in the absence of HBx...Ser-15 phosphorylation was pivotal, as E6AP could degrade p53 S15D (phosphomimetic mutant) but failed to act on p53 S15A (a non-phosphorylatable mutant). These findings suggest that HBx-induced p53 phosphorylation enhances E6AP-mediated degradation while concurrently inhibiting MDM2-mediated pathways, thereby fine-tuning p53 levels to support cell survival, viral replication and potentially carcinogenesis during HBV infection in human hepatocytes.
    Journal
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    CHEK2 (Checkpoint kinase 2)
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    TP53 mutation
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    etoposide IV • KU-55933
    3ms
    Mutation detection in women diagnosed with endometrial cancer: a next-generation sequencing analysis. (PubMed, Mol Cell Oncol)
    These findings highlight important molecular features of EC in Kurdish patients and may support future development of targeted therapeutic strategies. Further validation with larger cohorts is recommended.
    Journal • Next-generation sequencing
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    CHEK2 (Checkpoint kinase 2) • MUTYH (MutY homolog)
    3ms
    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, Cell Death Dis)
    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...Finally, the combination of a ClpP agonist with a known senolytic (venetoclax), synergistically increased the amount of cell death observed. In summary, we show that ClpP agonists stably induce an irreversible senescence in a ClpP-dependent manner that synergizes with venetoclax in TNBC cells.
    Journal
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    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CHEK2 (Checkpoint kinase 2) • TP53BP1 (Tumor Protein P53 Binding Protein 1)
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    Venclexta (venetoclax) • nesuparib (JPI-547) • Modeyso (dordaviprone) • TR57
    3ms
    Peruvoside, a cardiac glycoside, induces cell cycle arrest in non-small cell lung cancer (A549 cell line) and modulates PI3K/AKT/mTOR. (PubMed, J Complement Integr Med)
    Within this research, the data showed the arrest of the cell cycle and the inhibition of the proliferation regulatory gene by Peruvoside were associated with suppression of lung cancer survival, proliferation, metastatic dissemination, and promotion of cell death.
    Preclinical • Journal
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    mTOR (Mechanistic target of rapamycin kinase) • CCND1 (Cyclin D1) • CHEK2 (Checkpoint kinase 2) • CDK6 (Cyclin-dependent kinase 6) • CHEK1 (Checkpoint kinase 1) • PI3K (Phosphoinositide 3-kinases)
    3ms
    Rac1 GTPase Regulates the SCFβTrCP-Mediated Degradation of Claspin and the Cellular Response of Pancreatic Cancer Cells to Gamma Rays. (PubMed, Cancers (Basel))
    These findings identify Rac1 as a critical regulator of ATR/Chk1 signaling through stabilization of the fork protection protein Claspin. Rac1 inhibition promotes the βTrCP-dependent, proteasome-mediated degradation of Claspin via its phosphodegron, thereby impairing Chk1 activation in response to DNA damage.
    Journal
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    KRAS (KRAS proto-oncogene GTPase) • CHEK2 (Checkpoint kinase 2) • PLK1 (Polo Like Kinase 1) • RAC1 (Rac Family Small GTPase 1)
    3ms
    Sustained delivery of vemurafenib using polymeric nanocapsules induces apoptosis in anaplastic thyroid carcinoma (8305C cancer cells). (PubMed, Sci Rep)
    These findings suggest that delivering vemurafenib in polymeric nanocapsules produces delayed but sustained cytotoxic and apoptotic effects in ATC cells in vitro, warranting further investigation of this nanocarrier approach for thyroid cancer treatment. Altogether, the biological results reported in this study are derived from in vitro experiments and require further validation in in vivo models.
    Journal
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    TP53 (Tumor protein P53) • MDM2 (E3 ubiquitin protein ligase) • CHEK2 (Checkpoint kinase 2) • MDM4 (The mouse double minute 4) • CASP3 (Caspase 3) • CASP8 (Caspase 8) • CASP9 (Caspase 9) • ANXA5 (Annexin A5)
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    BRAF V600E • BRAF V600
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    Zelboraf (vemurafenib)
    3ms
    Spectrum of double heterozygosity in individuals diagnosed with hereditary breast and ovarian cancer. (PubMed, Eur J Cancer)
    Multiple heterozygosity in HBOC core genes is more frequent than previously assumed. Our data indicate that gene-gene constellations can reshape tumour phenotype and clinical severity rather than following single-gene expectations. Integrating multiple pVs into risk assessment and counselling may enhance personalised surveillance and risk-reducing strategies for DH individuals and their families in the era of widespread multigene testing.
    Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CHEK2 (Checkpoint kinase 2)
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    HR positive
    3ms
    Frequency of germline pathogenic variants in breast cancer predisposing genes in a national cohort of young women with breast cancer. (PubMed, Br J Cancer)
    Overall, 18.6% of women with young breast cancer had PVs in 18 genes tested, including 6.8% in a gene other than BRCA1 or BRCA2. Study results suggest that genetic testing should be offered to all women diagnosed breast cancer at the age of 40 or younger.
    Journal • BRCA Biomarker
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    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ATM (ATM serine/threonine kinase) • STK11 (Serine/threonine kinase 11) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • EPCAM (Epithelial cell adhesion molecule) • BARD1 (BRCA1 Associated RING Domain 1)
    3ms
    From Germline Susceptibility to Therapeutic Vulnerability: DNA Damage Response Gene Mutations Driving Multiple Myeloma Evolution and Precision Therapy. (PubMed, Hum Mutat)
    Moreover, DDR-associated vulnerabilities provide opportunities for precision therapies, including PARP inhibitor-based synthetic lethality strategies. This review summarizes the mechanistic and clinical significance of germline DDR alterations in MM and highlights their translational potential in precision oncology.
    Review • Journal • BRCA Biomarker • PARP Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CHEK2 (Checkpoint kinase 2)
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    BRCA2 mutation • BRCA1 mutation • ATM mutation • CHEK2 mutation
    3ms
    Hereditary Cancer Genetic Testing for All? A Retrospective Analysis on Genetic Mutations Found in Individuals Not Meeting NCCN® Guidelines. (PubMed, Eur J Breast Health)
    These findings support the potential value of expanded or universal genetic testing strategies, particularly in populations with limited family history or those outside current clinical criteria.
    Retrospective data • Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • SMAD4 (SMAD family member 4) • PMS2 (PMS1 protein homolog 2) • APC (APC Regulator Of WNT Signaling Pathway) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • MBD4 (Methyl-CpG Binding Domain 4, DNA Glycosylase) • MSH3 (MutS Homolog 3) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • MUTYH (MutY homolog) • FLCN (Folliculin) • POT1 (Protection of telomeres 1) • MITF (Melanocyte Inducing Transcription Factor) • SDHD (Succinate Dehydrogenase Complex Subunit D) • HOXB13 (Homeobox B13) • LZTR1 (Leucine Zipper Like Transcription Regulator 1) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)
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    ATM mutation • CHEK2 mutation • BRIP1 mutation • BARD1 mutation
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    CancerNext-Expanded®
    3ms
    Therapy-Induced Cellular Senescence in Non-Hodgkin Lymphomas, with Emphasis on Aggressive B-Cell Subtypes: Molecular Mechanisms and Emerging Drug Targets. (PubMed, Curr Cancer Drug Targets)
    In lymphomas, TIS is a dynamic stress-adaptation state that can support persistence and relapse. Rational integration of senescence biomarkers, timing-based therapies, and targeted senolytic/senomorphic interventions may enhance long-term treatment efficacy; however, most senescence-targeted strategies remain investigational and require lymphoma-specific clinical validation.
    Journal • IO biomarker
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    BCL2 (B-cell CLL/lymphoma 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • BCL2L1 (BCL2-like 1) • CHEK2 (Checkpoint kinase 2) • CHEK1 (Checkpoint kinase 1) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)