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    GENE:

    CHEK1 (Checkpoint kinase 1)

    i
    3d
    212Bi-Macroaggregated Albumin Inhibited Mouse Melanoma Growth by Regulating Cell Cycle Checkpoint Markers Without Promoting Living Cell Repopulation. (PubMed, J Nucl Med)
    Studies in mice showed that 212Bi-MAA was retained in B16F10 tumors and effectively reduced tumor growth in vivo without causing toxicity. These findings suggested that 212Bi-MAA was an effective therapy for mouse melanoma and did not induce factors that aid melanoma repopulation.
    Preclinical • Journal
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    CDH1 (Cadherin 1) • CHEK1 (Checkpoint kinase 1) • CASP3 (Caspase 3) • VIM (Vimentin) • CDH2 (Cadherin 2) • STAT1 (Signal Transducer And Activator Of Transcription 1) • NANOG (Nanog Homeobox)
    3d
    Biomarkers and potential function analysis of triple-negative breast cancer screening based on bioinformatics. (PubMed, Cancer Biomark)
    RT-qPCR analysis showed significant upregulation of CDO1, MCM4, DEPDC1, RRM2, and E2F1 in MDA-MB-231, CAL-148, and MFM-223 compared to MCF-10A. Our findings provide new insights into TNBC pathogenesis and potential therapeutic strategies, with important clinical implications for further understanding TNBC mechanisms and developing innovative treatments.
    Journal
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    TACC3 (Transforming acidic coiled-coil containing protein 3) • CHEK1 (Checkpoint kinase 1) • VEGFD (Vascular Endothelial Growth Factor D) • RRM2 (Ribonucleotide Reductase Regulatory Subunit M2) • MCM4 (Minichromosome Maintenance Complex Component 4) • E2F1 (E2F transcription factor 1)
    10d
    Study on the Mechanism of Formononetin Against Hepatocellular Carcinoma: Regulating Metabolic Pathways of Ferroptosis and Cell Cycle. (PubMed, Int J Mol Sci)
    In vivo, FM could inhibit tumor growth. FM could induce DNA damage leading to cell cycle arrest and may also induce ferroptosis by regulating glutathione metabolism, thereby intervening in the occurrence and development of HCC, making it a promising candidate for HCC treatment.
    Journal
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    CHEK1 (Checkpoint kinase 1) • GPX4 (Glutathione Peroxidase 4) • CDC25C (Cell Division Cycle 25C) • CDK1 (Cyclin-dependent kinase 1) • CCNB1 (Cyclin B1) • GNRP (Ras-Specific Guanine Nucleotide-Releasing Factor 1)
    12d
    Effect of PRKD3 on cell cycle in gastric cancer progression and downstream regulatory networks. (PubMed, Med Oncol)
    The overexpression of PRKD3 was intricately linked with the aggressive behaviors of GC. Targeting PRKD3 activity offers potential for effective treatments of GC.
    Journal
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    PLK1 (Polo Like Kinase 1) • CHEK1 (Checkpoint kinase 1) • CDK1 (Cyclin-dependent kinase 1) • CCNB1 (Cyclin B1)
    12d
    Checkpoint kinase 1 in colorectal cancer: Upregulation of expression and promotion of cell proliferation. (PubMed, World J Clin Oncol)
    Upregulation of CHEK1 promotes CRC cell proliferation. However, the dataset's diversity is limited, requiring further investigation into its specific mechanisms.
    Journal
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    CHEK1 (Checkpoint kinase 1)
    14d
    The Influence of Homologous Recombination Repair on Temozolomide Chemosensitivity in Gliomas. (PubMed, Carcinogenesis)
    Noteworthy efforts have been directed towards exploring inhibitors of these pathways in recent research endeavors, culminating in encouraging outcomes. In conclusion, the involvement of HRR in glioma resistance unveils novel therapeutic avenues, with targeting crucial molecules in the HRR pathway, holding promise for enhancing the effectiveness of TMZ therapy.
    Journal
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    HRD (Homologous Recombination Deficiency) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • CHEK1 (Checkpoint kinase 1)
    |
    temozolomide
    16d
    Crosstalk Between Plk1 and PTEN in Mitosis Affects Chromosomal Stability. (PubMed, DNA Cell Biol)
    PTEN has been described as an essential regulator of Plk1 for dephosphorylation and chromosomal stability during cell division, and Plk1 may directly interact with and phosphorylate PTEN at centromeres. Here, we review the bidirectional interplay between Plk1 and PTEN and how it contributes to genomic stability during mitosis.
    Review • Journal
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    ABL1 (ABL proto-oncogene 1) • PTEN (Phosphatase and tensin homolog) • PLK1 (Polo Like Kinase 1) • CHEK1 (Checkpoint kinase 1)
    19d
    Broussoflavonol B induces S-phase arrest and apoptosis in pancreatic cancer cells by modulating the cell cycle checkpoint through inhibition of the AURKA/PLK1 pathway. (PubMed, Cancer Cell Int)
    Bf-B might be a potent therapeutic agent for pancreatic cancer because of its ability to suppress the expression of AURKA/PLK1.
    Journal
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    AURKA (Aurora kinase A) • PLK1 (Polo Like Kinase 1) • CHEK1 (Checkpoint kinase 1) • CDC25C (Cell Division Cycle 25C) • CDK1 (Cyclin-dependent kinase 1) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • CCNB1 (Cyclin B1) • GNRP (Ras-Specific Guanine Nucleotide-Releasing Factor 1)
    20d
    Pan-cancer genetic profiles of mitotic DNA integrity checkpoint protein kinases. (PubMed, Cancer Biomark)
    However, further efforts are necessary to validate their clinical value for diagnosis and prognosis and to develop practical applications in clinical settings. Nevertheless, these pan-cancer profiles offer a better overall understanding as well as useful information for future reference regarding mitotic DNA integrity checkpoint signaling in cancer.
    Journal • BRCA Biomarker • Pan tumor
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    BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • PLK1 (Polo Like Kinase 1) • CHEK1 (Checkpoint kinase 1) • CDK2 (Cyclin-dependent kinase 2) • CDK1 (Cyclin-dependent kinase 1) • NEK11 (NIMA Related Kinase 11) • PLK2 (Polo Like Kinase 2) • PRKDC (Protein Kinase, DNA-Activated, Catalytic Subunit)
    21d
    Predictors of Radiation Resistance and Novel Radiation Sensitizers in Head and Neck Cancers: Advancing Radiotherapy Efficacy. (PubMed, Semin Radiat Oncol)
    Future directions emphasize personalized radiation therapy using genetics, sophisticated medication delivery systems, adaptive radiotherapy, and real-time monitoring. These integrated strategies seek to diminish radiation resistance and improve therapeutic efficacy in HNSCC.
    Review • Journal • BRCA Biomarker • PARP Biomarker • PD(L)-1 Biomarker • IO biomarker
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    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CHEK1 (Checkpoint kinase 1)
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    TP53 mutation • KRAS mutation • EGFR mutation
    21d
    Pericentriolar material 1 aggregation maintains cell survival upon prolonged replication stress. (PubMed, Arch Biochem Biophys)
    Prolonged replication stress induced DNA damage signaling via the ATM-CHK1 axis and autophagy to maintain cell survival, while PCM1 depletion alleviated ATM, CHK1, and autophagy activity, thereby reducing cell survival. Our findings propose that PCM1 does not facilitate centrosome amplification but instead induces activation of the ATM-CHK1 axis and autophagy to sustain osteosarcoma cell viability during prolonged replication stress.
    Journal
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    CHEK1 (Checkpoint kinase 1) • PCM1 (Pericentriolar Material 1) • PLK4 (Polo Like Kinase 4)
    23d
    Cyclin Y interacts with Chk1 to activate RRM2/STAT3 signaling and promotes radioresistance in non-small cell lung cancer. (PubMed, Int J Biol Sci)
    Rescue experiments confirm that the effects of Cyclin Y on lung cancer are mediated partially by RRM2. Collectively, we reveal for the first time that Cyclin Y promotes lung cancer radioresistance by binding to Chk1 to activate RRM2/STAT3 signaling, indicating that targeting Cyclin Y may be a promising strategy for enhancing the efficacy of radiotherapy in the treatment of non-small cell lung cancer.
    Journal
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    CHEK1 (Checkpoint kinase 1) • RRM2 (Ribonucleotide Reductase Regulatory Subunit M2)
    24d
    Spatio-Temporal Characterization of Cellular Senescence Hallmarks in Experimental Ischemic Stroke. (PubMed, Int J Mol Sci)
    Overall, our findings lend support to the existence of senescence after ischemic stroke in neurons and microglia/macrophages. However, there is still room to gain further insight into the role of senescence in the pathophysiology of ischemic stroke and in the implementation of successful senolytic therapy.
    Journal
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    IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • CHEK2 (Checkpoint kinase 2) • CHEK1 (Checkpoint kinase 1) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • IL1B (Interleukin 1, beta)
    24d
    ORCHID: Study of Olaparib in Metastatic Renal Cell Carcinoma Patients With DNA Repair Gene Mutations (clinicaltrials.gov)
    P2, N=20, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Mar 2026 --> Mar 2028 | Trial primary completion date: Mar 2025 --> Mar 2027
    Trial completion date • Trial primary completion date
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BAP1 (BRCA1 Associated Protein 1) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L)
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    ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • RAD54L mutation
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    Lynparza (olaparib)
    25d
    Glycyrrhizin enhances the antitumor activity of cisplatin in non‑small cell lung cancer cells by influencing DNA damage and apoptosis. (PubMed, Oncol Lett)
    In addition, western blotting analysis demonstrated that, in comparison with treatment with cisplatin or glycyrrhizin alone, the combined treatment markedly increased the protein expression levels of B-cell lymphoma 2-associated X protein, cleaved-caspase-3/caspase-3, γH2AX, phosphorylated-checkpoint kinase 1 and phosphorylated-p53/p53, while notably reducing the protein levels of B-cell lymphoma 2, cyclin D1, cyclin-dependent kinase 2 and cyclin-dependent kinase 4. The findings of the present study indicate that glycyrrhizin enhances the antitumor efficacy of cisplatin in non-small cell lung cancer cells by modulating DNA damage and apoptosis.
    Journal
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    BCL2 (B-cell CLL/lymphoma 2) • CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • CHEK1 (Checkpoint kinase 1) • CASP3 (Caspase 3) • CDK2 (Cyclin-dependent kinase 2)
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    cisplatin
    27d
    Replication stress: an early key event in ochratoxin a genotoxicity? (PubMed, Arch Toxicol)
    However, OTA did not appear to efficiently activate ATR-Chk1 and ATM-Chk2 DNA damage response pathways, suggesting that cells with under-replicated DNA or unresolved DNA damage may escape checkpoint control and may continue into mitosis, with potentially deleterious consequences for genomic integrity. Overall, results from this study provide first experimental evidence for perturbation of the S phase replisome machinery by OTA and point toward replication stress as an early key event in OTA genotoxicity.
    Journal
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    CHEK2 (Checkpoint kinase 2) • CHEK1 (Checkpoint kinase 1)
    28d
    Discovery of 4-(2-(methylamino)thiazol-5-yl)pyrimidin-2-amine derivatives as novel cyclin-dependent kinase 12 (CDK12) inhibitors for the treatment of esophageal squamous cell carcinoma. (PubMed, Bioorg Chem)
    In addition, H63 exhibited favorable pharmacokinetic properties, good safety, and prominent anti-ESCC activity in vivo. The present study suggests that CDK12 is a promising target for ESCC treatment, and H63 is a promising candidate for further clinical development as an anti-ESCC drug.
    Journal
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    CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • CHEK1 (Checkpoint kinase 1)
    30d
    Mono-ubiquitination of TopBP1 by PHRF1 enhances ATR activation and genomic stability. (PubMed, Nucleic Acids Res)
    Furthermore, conditional knockout of Phrf1 in mice leads to early lethality and impaired ATR-Chk1 axis signaling. Collectively, our findings establish PHRF1 as a novel E3 ligase for TopBP1, coordinating the replication stress response by enhancing TopBP1-ATR signaling.
    Journal
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    CHEK1 (Checkpoint kinase 1)
    1m
    Profiling genetic mutations in the DNA damage repair genes of oral squamous cell carcinoma patients from Pakistan. (PubMed, Sci Rep)
    TP53p.P33R was predominantly associated with moderately differentiated tumors (84.60%), naswar users (86.60%) and positive family history of cancer (91.60%). The TP53p.P33R, ATRp.M211T and CHEK1p.I437V mutations were found recurrently in 21/27 (77.7%), 20/27 (74.04%), and 27/27 (100%) patients, suggesting its potential biomarker applications in local screening.
    Journal
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    TP53 (Tumor protein P53) • CHEK2 (Checkpoint kinase 2) • CHEK1 (Checkpoint kinase 1)
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    TP53 mutation • ATM mutation • CHEK2 mutation • CHEK1 mutation
    1m
    Radiotherapy resistance driven by Asparagine endopeptidase through ATR pathway modulation in breast cancer. (PubMed, J Exp Clin Cancer Res)
    The newly identified AEP/ATR/PPP1R10 axis plays a dual role in genomic stability and radiotherapy resistance in BC. Our work provides new clues to the underlying mechanisms of tumor resistance and strong evidence validating the AEP/ATR axis as a novel predictive biomarker and therapeutic target for the stratification and treatment of radioresistant BC patients.
    Journal
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    CHEK1 (Checkpoint kinase 1)
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    cisplatin • etoposide IV
    1m
    EGFR tyrosine kinase inhibitor ZZC4 overcomes acquired resistance to gefitinib. (PubMed, Toxicol Appl Pharmacol)
    In this study, we developed NSCLC cells resistant to EGFR-TKI gefitinib and osimertinib and assessed the effect and mechanism of action of ZZC4 on those cells. Further, the proteomic analysis revealed that ZZC4 inhibited HCC827-GR cell growth by upregulating CDKN1B and downregulating CCNA2 and CHEK1. In conclusion, ZZC4 overcomes resistance to gefitinib by altering the cell cycle pathway.
    Preclinical • Journal
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    EGFR (Epidermal growth factor receptor) • CHEK1 (Checkpoint kinase 1) • CCNA2 (Cyclin A2) • CDKN1B (Cyclin dependent kinase inhibitor 1B)
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    Tagrisso (osimertinib) • gefitinib
    1m
    Targeting Chk1 and Wee1 kinases enhances radiosensitivity of 2D and 3D head and neck cancer models to X-rays and low/high-LET protons. (PubMed, Cell Death Dis)
    Here, we have analysed the response of head and neck squamous cell carcinoma (HNSCC) cell lines, spheroids and patient-derived organoids to X-rays and proton beam therapy (PBT) in the presence of either a Chk1 (MK-8776) or a Wee1 (MK-1775) inhibitor. We demonstrate that inhibitors of Chk1 or Wee1 can significantly enhance the radiosensitivity of both 2D and 3D models of HNSCC to X-rays and PBT (performed at both low and high ionisation densities), and that this effect is caused through abrogation of the G2/M checkpoint causing the persistence of DSBs. Our results therefore suggest that targeting Chk1 and Wee1 kinases in combination with X-rays and PBT could represent a promising therapeutic avenue to enhance the clinical efficacy of HNSCC treatment.
    Preclinical • Journal
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    CHEK1 (Checkpoint kinase 1)
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    adavosertib (AZD1775) • MK-8776
    1m
    The SUMOylated RREB1 interacts with KDM1A to induce 5-fluorouracil resistance via upregulating thymidylate synthase and activating DNA damage response pathway in colorectal cancer. (PubMed, MedComm (2020))
    Moreover, KDM1A knockdown improved the DNA damage and reduced RREB1-mediated resistance to 5-FU. These findings provide new insights into RREB1-mediated chemotherapy responses in CRC and indicate RREB1 is a potential target for overcoming 5-FU resistance.
    Journal
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    KDM1A (Lysine Demethylase 1A) • TYMS (Thymidylate Synthetase) • CHEK1 (Checkpoint kinase 1) • RREB1 (Ras Responsive Element Binding Protein 1)
    |
    5-fluorouracil
    2ms
    Cholangiocytes' Primary Cilia Regulate DNA Damage Response and Repair. (PubMed, bioRxiv)
    Deciliation was induced using shRNA knockdown or CRISPR knockout of IFT20, IFT88, or KIF3A, followed by exposure to the genotoxic agents cisplatin, methyl methanesulfonate (MMS), or irradiation...Deciliated cells exhibit heightened DNA damage, evidenced by increased γH2AX signals and comet assay results, a phenotype mirrored in in vivo IFT88 knockout mice. Furthermore, key DDR regulators, including ATM, p53, and p21, are downregulated in deciliated cells following irradiation, highlighting a crucial role for primary cilia in maintaining genome stability.
    Journal • PARP Biomarker
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    CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • CHEK1 (Checkpoint kinase 1) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
    |
    cisplatin
    2ms
    Combined inhibition of ribonucleotide reductase and WEE1 induces synergistic anticancer activity in Ewing's sarcoma cells. (PubMed, BMC Cancer)
    Our findings show that combined inhibition of RNR and WEE1 was effective against Ewing's sarcoma in vitro. They thus provide a rationale for the evaluation of the potential of combined targeting of RNR and WEE1 in Ewing's sarcoma in vivo.
    Journal • PARP Biomarker
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    CHEK1 (Checkpoint kinase 1) • CASP3 (Caspase 3) • CASP7 (Caspase 7)
    |
    TP53 mutation • TP53 wild-type
    |
    Lynparza (olaparib) • adavosertib (AZD1775) • veliparib (ABT-888) • azenosertib (ZN-c3) • Triapine (3-AP)
    2ms
    Comparative effects of arsenic trioxide and chemotherapy on Chk1 and CDC25 gene expression in gastric cancer cells AGS and MKN45: a potential therapeutic strategy. (PubMed, Mol Biol Rep)
    These findings highlight ATO's potential to sensitize GC cells to chemotherapy by impairing DNA repair mechanisms and inducing synergistic cytotoxicity. ATO holds promise as an adjuvant therapeutic agent for overcoming chemoresistance in gastric cancer.
    Clinical • Journal
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    CHEK1 (Checkpoint kinase 1) • RASGRF1 (Ras Protein Specific Guanine Nucleotide Releasing Factor 1) • GNRP (Ras-Specific Guanine Nucleotide-Releasing Factor 1)
    |
    IL2RA expression
    |
    docetaxel • oxaliplatin • arsenic trioxide
    2ms
    Advancement Opportunities and Endeavor of Innovative Targeted Therapies for Small Cell Lung Cancer. (PubMed, Int J Biol Sci)
    Moreover, the effectiveness of poly ADP-ribose polymerase and ataxia telangiectasia and rad3/checkpoint kinase 1 inhibitors is discussed and underscores the advantages of combining these inhibitors with standard chemotherapy to combat chemoresistance and enhance the antitumor effects of immunotherapies. Overall, this study investigates emerging strategies for targeted therapies and optimized combination regimens to overcome resistance in SCLC and highlights future strategies for new therapeutic technologies for SCLC.
    Review • Journal
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    DLL3 (Delta Like Canonical Notch Ligand 3) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • CHEK1 (Checkpoint kinase 1)
    2ms
    Pembrolizumab, Olaparib, and Temozolomide for People with Glioma (clinicaltrials.gov)
    P2, N=57, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Jan 2025 --> Jan 2026
    Trial completion date • Trial primary completion date
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    EGFR (Epidermal growth factor receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • FGFR (Fibroblast Growth Factor Receptor) • CDK12 (Cyclin dependent kinase 12) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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    CDKN2A deletion • BRIP1 mutation • RAD51C mutation • RAD51B mutation • BARD1 mutation • IDH wild-type
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    Keytruda (pembrolizumab) • Lynparza (olaparib) • temozolomide
    2ms
    Synergistic effect of inhibiting CHK2 and DNA replication on cancer cell growth. (PubMed, Elife)
    Importantly, it also prevented tumor development in xenografted NOD/SCID mice. The synergistic effect of inhibiting DNA replication and CHK2 signaling identifies a vulnerability of cancer cells that might be exploited by using clinically approved inhibitors in novel combination therapies.
    Journal
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    CHEK2 (Checkpoint kinase 2) • CHEK1 (Checkpoint kinase 1)
    2ms
    Phase II Study of PARP Inhibitor Olaparib and IV Ascorbate in Castration Resistant Prostate Cancer (clinicaltrials.gov)
    P2, N=4, Terminated, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | N=15 --> 4 | Trial completion date: Mar 2028 --> Oct 2024 | Recruiting --> Terminated | Trial primary completion date: Mar 2028 --> Oct 2024; The study was terminated by the IRB due to low accrual,
    Enrollment change • Trial completion date • Trial termination • Trial primary completion date
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L)
    |
    FoundationOne® Liquid CDx
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    Lynparza (olaparib)
    2ms
    OPTIMUM: Olaparib with or Without Durvalumab for DDR Gene Mutated Biliary Tract Cancer Following Platinum-based Chemotherapy (clinicaltrials.gov)
    P2, N=62, Recruiting, Asan Medical Center | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2025
    Trial completion date • Trial primary completion date
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • POLE (DNA Polymerase Epsilon) • BAP1 (BRCA1 Associated Protein 1) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • BRCA (Breast cancer early onset) • 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) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • XRCC2 (X-Ray Repair Cross Complementing 2) • FANCD2 (FA Complementation Group D2) • GEN1 (GEN1 Holliday junction 5' flap endonuclease)
    |
    ATM mutation • CHEK2 mutation • BRIP1 mutation • BARD1 mutation
    |
    Lynparza (olaparib) • Imfinzi (durvalumab)
    2ms
    Targeting Metabolic and Epigenetic Vulnerabilities in Glioblastoma with SN-38 and Rabusertib Combination Therapy. (PubMed, Int J Mol Sci)
    A significant obstacle in treating GBM is the expression of O6-methylguanine-DNA methyltransferase, a DNA repair enzyme that reduces the efficacy of the standard alkylating agent, temozolomide, in about 50% of patients. Reduced intermediates of the glutathione cycle indicated increased cellular stress following combinatorial treatment. Overall, the combination of SN-38 and rabusertib synergistically disrupts metabolites associated with epigenetic adaptations, leading to cytotoxicity independent of O6-methylguanine-DNA methyltransferase status, thereby underpinning this combination as a promising candidate for combinatorial therapy in GBM.
    Journal
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    CHEK1 (Checkpoint kinase 1)
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    temozolomide • rabusertib (LY 2603618)
    2ms
    Gemcitabine and ATR inhibitors synergize to kill PDAC cells by blocking DNA damage response. (PubMed, Mol Syst Biol)
    Here, we phenotypically screened 13 human pancreatic adenocarcinoma (PDAC) cell lines against GEM in combination with 146 clinical inhibitors and observed strong synergy for the ATR kinase inhibitor Elimusertib in most cell lines. Dose-dependent phosphoproteome profiling of four ATR inhibitors following DNA damage induction by GEM revealed a strong block of the DNA damage response pathway, including phosphorylated pS468 of CHEK1, as the underlying mechanism of drug synergy. The current work provides a strong rationale for why the combination of GEM and ATR inhibition may be useful for the treatment of PDAC patients and constitutes a rich phenotypic and molecular resource for further investigating effective drug combinations.
    Journal
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    CHEK1 (Checkpoint kinase 1)
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    gemcitabine • elimusertib (BAY 1895344)
    3ms
    BIBR1532 inhibits proliferation and metastasis of esophageal squamous cancer cells by inducing telomere dysregulation. (PubMed, World J Gastrointest Oncol)
    BIBR1532 exerts anti-cancer effects on ESCC by inducing DDR through the ATR/CHK1 and ATM/CHK2 pathways and downregulating the expression of telomere-binding proteins.
    Journal
    |
    TERT (Telomerase Reverse Transcriptase) • CHEK2 (Checkpoint kinase 2) • ATR (Ataxia telangiectasia and Rad3-related protein) • CHEK1 (Checkpoint kinase 1) • POT1 (Protection of telomeres 1) • TERF1 (Telomeric Repeat Binding Factor 1) • TERF2 (Telomeric Repeat Binding Factor 2)
    |
    ATM expression
    |
    BIBR1532
    3ms
    Targeting CHEK1: Ginsenosides-Rh2 and Cu2O@G-Rh2 nanoparticles in thyroid cancer. (PubMed, Cell Biol Toxicol)
    Cu2O@G-Rh2 nanoparticles possess excellent stability and anti-tumor efficacy. This research offers new perspectives for the treatment of THCA and demonstrates potential clinical applications.
    Journal
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    CHEK1 (Checkpoint kinase 1)
    3ms
    WEE1 Inhibition by AZD1775 Augments Colorectal Cancer Cells Susceptibility to VE-822-induced DNA Damage and Apoptosis. (PubMed, Drug Res (Stuttg))
    DNA damage markers, including γ-H2AX and 8-oxo-dG were upregulated in these cells. Simultaneous treatment with VE-822 and AZD177 increased apoptosis capacity of both cell lines.The inhibition of WEE1 via AZD1775 potentiated the anticancer effects of ATR inhibitor, VE-822, in combating colorectal cancer via targeting DNA damage.
    Journal
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    CHEK1 (Checkpoint kinase 1) • RRM1 (Ribonucleotide Reductase Catalytic Subunit M1) • RRM2 (Ribonucleotide Reductase Regulatory Subunit M2)
    |
    adavosertib (AZD1775) • berzosertib (M6620)
    3ms
    Beyond the Horizon: Rethinking Prostate Cancer Treatment Through Innovation and Alternative Strategies. (PubMed, Cancers (Basel))
    In due course, this results first in a pro-survival quiescence and then adaptation to ADT and CRPC progression. This constitutes a novel liability for PCa that we have targeted for several years and novel approaches.
    Journal
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    CHEK1 (Checkpoint kinase 1) • NEK1 (NIMA Related Kinase 1) • TLK1 (Tousled Like Kinase 1)
    |
    AR overexpression
    3ms
    The Synergistic Effect of PARP Inhibitors and Irinotecan in Small Cell Lung Cancer Cells. (PubMed, Cancer Res Treat)
    When treated with 50 nM irinotecan, the IC50 fold changes for PARP inhibitors were: olaparib, 1649 ± 4049; talazoparib, 25 ± 34.21; venadaparib, 336 ± 596.01. This study provides preclinical evidence of the potential clinical benefits of combining irinotecan with PARP inhibitors in SCLC. Further clinical investigations are warranted to validate these findings for the development of more effective and personalized therapeutic strategies for SCLC patients.
    Journal • BRCA Biomarker • PARP Biomarker
    |
    BRCA (Breast cancer early onset) • CHEK1 (Checkpoint kinase 1)
    |
    BRCA mutation
    |
    Lynparza (olaparib) • Talzenna (talazoparib) • irinotecan • venadaparib (NOV 1401)
    3ms
    Niraparib Before Surgery in Treating Patients With High Risk Localized Prostate Cancer and DNA Damage Response Defects (clinicaltrials.gov)
    P2, N=30, Recruiting, Marc Dall'Era, MD | Trial completion date: Feb 2025 --> Jun 2025 | Trial primary completion date: Aug 2024 --> Jun 2025
    Trial completion date • Trial primary completion date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • 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) • CHEK1 (Checkpoint kinase 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCL (FA Complementation Group L) • FANCD2 (FA Complementation Group D2) • GEN1 (GEN1 Holliday junction 5' flap endonuclease)
    |
    Zejula (niraparib)
    3ms
    Formation of reactive species via high power microwave induced DNA damage and promoted intrinsic pathway-mediated apoptosis in lung cancer cells: An in vitro investigation. (PubMed, Fundam Res)
    These findings clarify the cellular mechanisms underlying HPM-induced cell death, potentially advancing therapeutic approaches for treating NSCLC, and a useful first step for future investigations in this area. Moreover, this technique has the potential to serve as an adjunct to non-surgical methods in cancer therapy.
    Preclinical • Journal
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    CHEK2 (Checkpoint kinase 2) • CHEK1 (Checkpoint kinase 1)
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    ATM expression
    3ms
    Unveiling the substantial role of rutin in the management of drug-induced nephropathy using network pharmacology and molecular docking. (PubMed, Int Immunopharmacol)
    The revelation of mode of action of bioactive constituent rutin against drug-induced nephropathy provides a theoretical basis for designing more promising compounds in future for treatment of nephropathy.
    Journal
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    EGFR (Epidermal growth factor receptor) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • MCL1 (Myeloid cell leukemia 1) • KDR (Kinase insert domain receptor) • ABCG2 (ATP Binding Cassette Subfamily G Member 2) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • PIK3CG (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Gamma) • PRKCH (Protein Kinase C Eta) • IL2 (Interleukin 2) • PLK1 (Polo Like Kinase 1) • CHEK1 (Checkpoint kinase 1) • SYK (Spleen tyrosine kinase) • PTGS2 (Prostaglandin-Endoperoxide Synthase 2) • ALDH2 (Aldehyde Dehydrogenase 2 Family Member) • IR (Insulin receptor) • MMP9 (Matrix metallopeptidase 9) • SERPINE1 (Serpin Family E Member 1) • CDK1 (Cyclin-dependent kinase 1) • CXCR1 (Chemokine (C-X-C motif) receptor 1) • HSD17B2 (Hydroxysteroid 17-Beta Dehydrogenase 2) • MAPT (Microtubule Associated Protein Tau) • NOX4 (NADPH Oxidase 4) • PDE5A (Phosphodiesterase 5A) • PRKACA (Protein Kinase CAMP-Activated Catalytic Subunit Alpha) • PRKCA (Protein Kinase C Alpha) • PRKCB (Protein Kinase C Beta) • CYP1B1 (Cytochrome P450 Family 1 Subfamily B Member 1) • KCNH2 (Potassium Voltage-Gated Channel Subfamily H Member 2) • MMP3 (Matrix metallopeptidase 3) • PACERR (PTGS2 Antisense NFKB1 Complex-Mediated Expression Regulator RNA)
    3ms
    The histone H3.3 K27M mutation suppresses Ser31phosphorylation and mitotic fidelity, which can directly drive gliomagenesis. (PubMed, Curr Biol)
    Replication-competent avian leukosis virus splice-acceptor (RCAS)/cellular receptor for subgroup A avian sarcoma and leukosis virus (TVA) mice expressing S31A also form diffuse midline gliomas morphologically indistinguishable from K27M tumors. Together, our results reveal that the H3.3 K27M mutant alters H3.3 Ser31 phosphorylation, which, in turn, has profound impacts on chromosome segregation/cell-cycle regulation.
    Journal
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    TP53 (Tumor protein P53) • CHEK1 (Checkpoint kinase 1)
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    TP53 mutation