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    GENE:

    CHEK2 (Checkpoint kinase 2)

    i
    Other names: CHEK2, bA444G7, CDS1, CHK2, HuCds1, PP1425, RAD53, Checkpoint kinase 2
    2d
    PARP inhibitors in testicular germ cell tumors: what we know and what we are looking for. (PubMed, Front Genet)
    However, few responses to PARPis in TGCTs have been detected in patients with BRCA1/2, ATM or CHEK2 mutations, reinforcing the idea that patients should be optimally selected for tailored treatments in the era of personalized medicine. Future preclinical and clinical research is needed to further investigate the molecular mechanisms of cisplatin resistance and to identify novel therapeutic strategies in resistant/refractory TGCTs patients.
    Review • Journal • BRCA Biomarker • PARP Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • CHEK2 (Checkpoint kinase 2)
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    CHEK2 mutation
    |
    cisplatin
    5d
    Characterization of the BH1406 non-small cell lung cancer (NSCLC) cell line carrying an activating SOS1 mutation. (PubMed, Transl Lung Cancer Res)
    Besides BAY-293, BH1406 cells proved to be sensitive to the SOS1 inhibitors MRTX0902 and BI-3406...Additionally, the PI3K inhibitor dactolisib, the GSK-3 inhibitor BI-5521 as well as the bromodomain protein-directed PROTAC ARV-771 inhibited the growth of BH1406 cells significantly and showed synergistic interaction with BAY-293...BH1406 cells represent a novel cellular model suitable for the molecular characterization of SOS1 druggability. Such rare oncogenic driver genes are not included in standard NGS panels and need to be detected by expanded assays like WES.
    Preclinical • Journal
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    CHEK2 (Checkpoint kinase 2) • STAT3 (Signal Transducer And Activator Of Transcription 3) • SOS1 (SOS Ras/Rac Guanine Nucleotide Exchange Factor 1)
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    MYC expression
    |
    Lung Cancer Mutation Panel
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    dactolisib (RTB101) • BI-3406 • MRTX0902
    5d
    Increased frequency of CHEK2 germline pathogenic variants among individuals with dermatofibrosarcoma protuberans. (PubMed, Genet Med Open)
    This study of multiple cohorts identifies CHEK2 as a candidate susceptibility gene for DFSP. Additional epidemiologic and functional studies are needed to further characterize this potential gene-tumor relationship.
    Journal
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    TP53 (Tumor protein P53) • ERCC1 (Excision repair cross-complementation group 1) • CHEK2 (Checkpoint kinase 2) • ERCC5 (ERCC Excision Repair 5 Endonuclease 2) • MUTYH (MutY homolog) • DOCK8 (Dedicator Of Cytokinesis 8) • RECQL4( RecQ Like Helicase 4)
    5d
    Combining rare and common genetic variants improves population risk stratification for breast cancer. (PubMed, Genet Med Open)
    Moreover, women with a pLOF in ATM or CHEK2 and ranking in the top 50% of the PRS displayed a high risk (39.2% probability of breast cancer at age 70), whereas their counterparts in the bottom 50% of the PRS were not at high risk (14.4% probability at age 70). Our findings suggest that a combined monogenic and polygenic approach allowed a better identification of participants with high risk while minimizing false positives.
    Journal
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2)
    5d
    Cancer burden in individuals with single versus double pathogenic variants in cancer susceptibility genes. (PubMed, Genet Med Open)
    Individuals with ATM+CHEK2 or 2 CHEK2 PVs have a greater cancer burden than single gene controls. These findings can be used to counsel individuals with DPVs and their families and inform cancer screening recommendations.
    Journal
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2)
    6d
    Prevalence and Distribution of Unexpected Actionable Germline Pathogenic Variants Identified on Broad-Based Multigene Panel Testing Among Patients With Cancer. (PubMed, JCO Precis Oncol)
    In patients with cancer, MGPT identified a rate of 1.7% PV in unexpected actionable cancer predisposition genes. Findings were more often unexpected (2.8%) when considering only the patient cancer history. These findings may justify consideration of broader MGPT panels in patients with cancer, given implications for subsequent surveillance, cascade testing, and treatment options dependent on specific findings.
    Retrospective data • Journal • BRCA Biomarker
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    TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • MSH6 (MutS homolog 6) • PMS2 (PMS1 protein homolog 2) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • MITF (Melanocyte Inducing Transcription Factor) • SDHC (Succinate Dehydrogenase Complex Subunit C) • HOXB13 (Homeobox B13) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)
    8d
    Search for germline gene variants in colorectal cancer families presenting with multiple primary colorectal cancers. (PubMed, Int J Cancer)
    In the nine whole-exome sequenced patients, eight harbored at least two candidate DNA repair/cell cycle/TGFβ signaling gene variants. The number of families is too small to provide evidence for individual variants but, considering the known role of DNA repair/cell cycle genes in CRC, the clustering of multiple deleterious variants in the present families suggests that these, perhaps jointly, contributed to CRC development in these families.
    Journal
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    CHEK2 (Checkpoint kinase 2) • FANCI (FA Complementation Group I) • RECQL5 (RecQ Like Helicase 5) • RRM2 (Ribonucleotide Reductase Regulatory Subunit M2) • RECQL (RecQ Like Helicase) • XRCC1 (X-Ray Repair Cross Complementing 1) • FAAP24 (FA Core Complex Associated Protein 24)
    9d
    Measuring the Effects of Talazoparib in Patients With Advanced Cancer and DNA Repair Variations (clinicaltrials.gov)
    P2, N=36, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2026
    Trial completion date • Trial primary completion date • Metastases
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    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) • BAP1 (BRCA1 Associated Protein 1) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • 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)) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCF (FA complementation group F) • FANCL (FA Complementation Group L) • FANCI (FA Complementation Group I) • FANCM (FA Complementation Group M) • BACH1 (BTB Domain And CNC Homolog 1) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • FANCB (FA Complementation Group B) • FANCC (FA Complementation Group C)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation
    |
    Talzenna (talazoparib)
    9d
    Chemically synthesized CdSe quantum dots induce apoptosis in AGS gastric cancer cells via ROS generation. (PubMed, Nanoscale Adv)
    More importantly, it has been demonstrated that CdSe QDs promote excessive production of ROS in AGS cells, which is believed to be the cause of apoptosis and the reduction of cell proliferation. These data suggest that CdSe QDs are a good candidate for combating gastric cancer cells.
    Journal
    |
    CHEK2 (Checkpoint kinase 2)
    11d
    A missense variant effect map for the human tumor-suppressor protein CHK2. (PubMed, Am J Hum Genet)
    It also provides strong evidence toward pathogenicity for some clinical missense variants and supporting evidence toward benignity for others. Overall, this comprehensive missense variant effect map contributes to understanding of both known and yet-to-be-observed CHK2 variants.
    Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • CHEK2 (Checkpoint kinase 2)
    12d
    A phase II study evaluating safety and efficacy of niraparib in patients with previously treated homologous recombination defective metastatic esophageal/gastroesophageal junction/proximal gastric adenocarcinoma. (PubMed, Front Oncol)
    The most common adverse events seen were anemia, fatigue, and thrombocytopenia. In patients with metastatic EAC, single agent niraparib as second line therapy is not an effective option.
    P2 data • Journal • Metastases
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ARID1A (AT-rich interaction domain 1A) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • GEN1 (GEN1 Holliday junction 5' flap endonuclease) • PARP2 (Poly(ADP-Ribose) Polymerase 2)
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    FANCA deletion
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    Zejula (niraparib)
    12d
    Drug Repurposing Screen for the Rare Disease Ataxia-Telangiectasia. (PubMed, SLAS Discov)
    Over 6,000 compounds from small molecule drug repurposing libraries were subsequently screened in the assay developed, leading to identification of several promising in vitro hits. Using the assay developed and the identified hits opens avenues to investigate potential therapeutics for A-T.
    Journal
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    CHEK2 (Checkpoint kinase 2)
    15d
    Phase II Trial of the PARP Inhibitor, Niraparib, in BAP1 and Other DNA Damage Response Pathway-Deficient Neoplasms. (PubMed, JCO Precis Oncol)
    Niraparib failed to meet the prespecified efficacy end point for response. However, clinical benefit was suggested in a proportion of patients who had a confirmed mBAP1, supporting further investigation.
    P2 data • Journal • BRCA Biomarker • PARP Biomarker
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    PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD50 (RAD50 Double Strand Break Repair Protein)
    |
    PTEN mutation • ARID1A mutation • BAP1 mutation
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    Zejula (niraparib)
    15d
    Genetic Testing and Analysis in Breast Cancer Patients in Greece. (PubMed, Cureus)
    Genetic testing following National Comprehensive Cancer Network (NCCN) guidelines offers valuable insights for patients and their families. This information enhances counseling and identifying germline PVs could refine treatment strategies, potentially improving prognostic outcomes.
    Journal • BRCA Biomarker
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSH2 (MutS Homolog 2) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1)
    17d
    The molecular landscape of 227 adult granulosa cell tumors of the ovary: Insights into the progression from primary to recurrence. (PubMed, Lab Invest)
    One tumor exhibited MSI-High status and a TMB of 19 mut/Mb. Our results indicate the need for further investigation into the role of FOXO1 as a potential prognostic marker in AGCTs.
    Journal • MSi-H Biomarker
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    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • TERT (Telomerase Reverse Transcriptase) • KMT2D (Lysine Methyltransferase 2D) • CHEK2 (Checkpoint kinase 2) • DICER1 (Dicer 1 Ribonuclease III) • FOXL2 (Forkhead Box L2)
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    TP53 mutation • KRAS mutation • MSI-H/dMMR • PIK3CA mutation • CHEK2 mutation • TERT mutation • TERT promoter mutation
    20d
    Optimizing and Validating Systemic DNA Damage Response Profiling to Predict Neoadjuvant Chemoradiation Response in Rectal Cancer. (PubMed, medRxiv)
    This assay uses a Luminex xMAP platform to detect DNA damage response (DDR) signaling proteins in peripheral blood monocytes of pre-treatment patients. This assay, detecting the DDR proteins, effectively segregates responders from non-responders (p ≤ 1e-5), supporting optimization of treatment efficacy and reduction of unnecessary toxicity, thus advancing personalized medicine in oncology.
    Journal
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    CHEK2 (Checkpoint kinase 2) • CHEK1 (Checkpoint kinase 1) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
    21d
    Molecular and In Silico Analysis of the CHEK2 Gene in Individuals with High Risk of Cancer Predisposition from Türkiye. (PubMed, Cancers (Basel))
    This comprehensive analysis of CHEK2 variants in the Turkish population provides crucial insights for cancer geneticists and oncologists. Our findings will help to enhance the evaluation and management of cancer predisposition associated with CHEK2 in Türkiye and other regions that have significant Turkish populations.
    Journal
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    CHEK2 (Checkpoint kinase 2) • ARG1 (Arginase 1)
    21d
    Prospective Screening of Cancer Syndromes in Patients with Mesenchymal Tumors. (PubMed, Cancers (Basel))
    We conclude that second-hit analyses can be used in standard of care to identify syndrome-related tumors. This approach can help distinguish true manifestations of tumor syndromes from unrelated germline findings and enhance the understanding of germline predisposition in soft tissue tumors. Prospective screening using germline whole genome sequencing should be considered when comprehensive somatic sequencing is introduced into clinical practice.
    Journal • IO biomarker
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    TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • CHEK2 (Checkpoint kinase 2) • KCNQ1OT1 (KCNQ1 Opposite Strand/Antisense Transcript 1) • SDHC (Succinate Dehydrogenase Complex Subunit C) • CDC73 (Cell Division Cycle 73)
    22d
    Germline Variant Spectrum in Southern Italian High-Risk Hereditary Breast Cancer Patients: Insights from Multi-Gene Panel Testing. (PubMed, Curr Issues Mol Biol)
    Variants of uncertain significance were detected in 20% of patients, emphasizing the ongoing challenge of variant interpretation in the era of multi-gene panel testing. These findings not only enhance our understanding of the genetic landscape of breast cancer in Southern Italy but also provide a foundation for developing more targeted, population-specific approaches to genetic testing and counseling, ultimately contributing to the advancement of precision medicine in oncology.
    Journal • BRCA Biomarker
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    TP53 (Tumor protein P53) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C)
    |
    RAD51C mutation
    22d
    PEPN2112: Elimusertib for the Treatment of Relapsed or Refractory Solid Tumors (clinicaltrials.gov)
    P1/2, N=31, Active, not recruiting, National Cancer Institute (NCI) | N=23 --> 31 | Trial completion date: Dec 2024 --> Nov 2025 | Trial primary completion date: Dec 2024 --> Sep 2024
    Enrollment change • Trial completion date • Trial primary completion date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • MSH2 (MutS Homolog 2) • CDK12 (Cyclin dependent kinase 12) • WT1 (WT1 Transcription Factor) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • POLD1 (DNA Polymerase Delta 1) • FOXO1 (Forkhead box O1) • XRCC2 (X-Ray Repair Cross Complementing 2) • ATF1 (Activating Transcription Factor 1) • PAX3 (Paired Box 3)
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    elimusertib (BAY 1895344)
    23d
    Homologous recombination deficiency in pancreatic neuroendocrine tumors. (PubMed, Future Oncol)
    However, thanks to the SNP analysis, a consistent number of partial or complete single-copy deletions or duplications in several chromosomes. The AmoyDX HRD focus assay performed well on pancreatic samples, despite being originally designed for ovarian cancer and used on samples stored for over a year. Larger studies are needed to further assess the role of HRD assays in pNETs research.
    Journal • BRCA Biomarker
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    BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • MUTYH (MutY homolog)
    |
    HRD • CHEK2 mutation
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    AmoyDx® HRD Focus Panel
    27d
    Association between homologous recombination deficiency and time to treatment failure to platinum-based chemotherapy for pancreatic cancer by using the C-CAT database. (PubMed, J Gastroenterol)
    Our findings suggest that HRR-related genetic abnormalities might be predictive of TTF in platinum-based chemotherapy for PC.
    Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)
    |
    HRD • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • BARD1 mutation
    |
    FoundationOne® CDx • OncoGuide™ NCC Oncopanel System
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    gemcitabine • 5-fluorouracil • albumin-bound paclitaxel • irinotecan • leucovorin calcium
    27d
    Light and shade of multigene panel testing for hereditary cancer: Examples from the real world. (PubMed, Tumori)
    Furthermore, for some of the genes included in MGPT, for instance NBN, the association with cancer risk has been questioned, leading to potentially misleading results. Taken together, the cases here described provide some examples of the benefits, as well as risks, involved by the use of MGPT, which may increase awareness among users and reinforce the need for establishing clear recommendations on genes to be included and management of the results.
    Journal • Real-world evidence • Real-world
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    ATM (ATM serine/threonine kinase) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))
    28d
    Hereditary breast and ovarian cancer genetic testing in unselected patients: example of private supplementation of public healthcare service. (PubMed, Fam Cancer)
    Out of 177 patients referred to our center who underwent BRCA1/2 testing, 175 tested negative while two (1.1%) resulted carriers of pathogenic variants in BRCA2; 69 patients also underwent MGPT, and in four cases (5.8%) a pathogenic variant were found (two in ATM and one in CHEK2 and RAD51C, respectively). Overall, this private supplementation of territorial public healthcare system has made it possible to confirm the validity of regional criteria for genetic testing access (concordance: 98.9%), but also to identify carriers of pathogenic variants of BRCA1/2 that would have escaped regional protocol, to support the effectiveness of MGPT for the identification of rare cases (not BRCA) at mild/high risk, and to provide reassurance to women who were found to be non-carriers of pathogenic variants, who may benefit from a more accurate assessment of their risk.
    Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C)
    1m
    p53 pathway genes’ mutations (muts) as prognostic factors in patients (pts) with metastatic Pancreatic Ductal Adenocarcinoma (mPDAC): a single center study (AIOM 2024)
    Our study suggests an important prognostic role of p53 signaling muts in mPDAC pts; wt pts resulted in a longer OS than mutated pts, although some muts, in particular tp53 exon4 mut, seem to be associated with longer survival. Further studies are needed to investigate these findings, including an in-depth analysis of structural proteomics.
    Clinical • Metastases
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    KRAS (KRAS proto-oncogene GTPase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • CHEK2 (Checkpoint kinase 2) • MDM4 (The mouse double minute 4) • CHEK1 (Checkpoint kinase 1) • TP53BP1 (Tumor Protein P53 Binding Protein 1)
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    TP53 mutation • KRAS mutation • TP53 wild-type • TP53 exon 4 mutation
    |
    TruSight Oncology 500 Assay
    1m
    Mismatch Repair (MMR) and Homologous Recombination (HR) Deficiency: Real-Life Applications of biomarkers for complementary approaches in Epithelial Ovarian Cancer (AIOM 2024)
    HRD genomic instability tests and multigene panel assessments serve as synergistic tools in EOC clinical settings, proving essential for identifying patients likely to benefit from PARPi therapy. These tools also enhance the detection of HRR and MMR gene variants, aiding in preventive care. Further investigations into the genetic profiles of HRD-negative tumors are crucial for advancing cancer risk management and developing novel therapeutic avenues.
    Clinical • Mismatch repair • BRCA Biomarker • PARP Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • PMS2 (PMS1 protein homolog 2) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • MUTYH (MutY homolog)
    |
    BRCA2 mutation • BRCA1 mutation • HRD • BRCA wild-type
    |
    Myriad myChoice® CDx
    1m
    Homologous recombination (HR) and DNA damage repair (DDR) somatic alterations in metastatic colorectal cancer (mCRC): results from the comprehensive genomic profiling (CGP) trial FPG500 (AIOM 2024)
    Background : Treatment (tx) of MSS/MMRp mCRC relies mainly on oxaliplatin (oxa)- or irinotecan-based doublet chemotherapy regimens, with no biomarker reported so far, allowing the selection of one tx over the other. HR-DDRa is associated with MSI-H or TMB-H. Pts with MSS HR-DDRa tumors benefit from oxa-based first line treatment. Longer FU, allowing mature OS data, and wider cohorts are warranted.
    Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker • Metastases
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    TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD50 (RAD50 Double Strand Break Repair Protein) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCL (FA Complementation Group L) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)
    |
    TMB-H • MSI-H/dMMR
    |
    TruSight Oncology 500 Assay
    |
    oxaliplatin • irinotecan
    1m
    Germline pathogenic variants in prostate cancer. (PubMed, Pathol Res Pract)
    Individuals with a family history of cancer were significantly more likely to have a pathogenic or likely pathogenic variant than those without one (p = 0.002). Overall, our results show the necessity for future research with a larger sample size to better explain the relationship between clinicopathologic data and genetic variants.
    Journal • BRCA Biomarker
    |
    TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • MUTYH (MutY homolog) • HOXB13 (Homeobox B13) • LZTR1 (Leucine Zipper Like Transcription Regulator 1)
    1m
    Guarding against digestive-system cancers: Unveiling the role of Chk2 as a potential therapeutic target. (PubMed, Genes Dis)
    In addition, we summarize evidence indicating that Chk2 can serve as a novel therapeutic target, based on its contributions to radiochemotherapy-resistance reversion and progress made in developing antitumor agents against Chk2. The prevailing evidence supports the conclusion that further research on Chk2 will provide a deeper understanding of digestive-system tumorigenesis and should suggest novel therapeutic targets.
    Review • Journal
    |
    CHEK2 (Checkpoint kinase 2)
    1m
    A case of a patient at reproductive age with BRCA2 and CHEK2 mutations and multiple uterine fibroids. (PubMed, Ginekol Pol)
    No abstract available
    Journal • BRCA Biomarker
    |
    BRCA2 (Breast cancer 2, early onset) • CHEK2 (Checkpoint kinase 2)
    |
    CHEK2 mutation • BRCA2 mutation + CHEK2 mutation
    1m
    Pathogenic variants in cancer susceptibility genes predispose to Ductal Carcinoma In situ of the breast. (PubMed, Clin Cancer Res)
    The enrichment of PVs in ATM, BRCA1, BRCA2, CHEK2 and PALB2 among women with DCIS suggests that multigene panel testing may be appropriate for women with DCIS. Elevated risks of contralateral breast cancer in carriers of PVs in high penetrance genes with DCIS confirmed the utility of testing for surgical decision-making.
    Journal • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • PALB2 (Partner and localizer of BRCA2) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)
    1m
    Panobinostat Synergizes with Chemotherapeutic Agents and Improves Efficacy of Standard-of-Care Chemotherapy Combinations in Ewing Sarcoma Cells. (PubMed, Cancers (Basel))
    The combination of Panobinostat with Doxorubicin or Etoposide, both of which are used as standard of care in upfront treatment, leads to a synergistic effect in EWS cells. Overall, our data indicate that HDAC2 is overexpressed in many EWS tumor samples and HDAC inhibition is effective in targeting EWS cells, alone and in combination with standard-of-care chemotherapy agents. This work suggests that the addition of an HDAC inhibitor to upfront treatment may improve response.
    Journal
    |
    ALK (Anaplastic lymphoma kinase) • CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • CHEK2 (Checkpoint kinase 2) • JAK1 (Janus Kinase 1) • CHEK1 (Checkpoint kinase 1) • CASP3 (Caspase 3) • HDAC2 (Histone deacetylase 2)
    |
    CCND1 expression • HDAC2 expression
    |
    doxorubicin hydrochloride • etoposide IV • Farydak (panobinostat)
    1m
    BRCA2 and TP53 Mutations in a Breast Cancer Patient: A Case Report and Review of the Literature. (PubMed, Cureus)
    Multigene tests are essential in the treatment approach to young BC patients, since the detection of specific mutations may help guide changes in preventive measures and treatment plans. This report describes a rare case of BC in a young patient with pathogenic germline variants in BRCA2 and TP53 genes and also presents a literature review of the topic.
    Review • Journal • BRCA Biomarker
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2)
    |
    TP53 mutation • BRCA2 mutation + TP53 mutation
    1m
    PLATPARP: A Trial of Niraparib in Platinum-Sensitive Castration-Resistant Prostate Cancer with DNA Repair Defects (clinicaltrials.gov)
    P2, N=12, Completed, Abramson Cancer Center at Penn Medicine | Active, not recruiting --> Completed | Trial completion date: Jun 2024 --> Feb 2024 | Trial primary completion date: Jun 2024 --> Feb 2024
    Trial completion • Trial completion date • Trial primary completion date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • HDAC2 (Histone deacetylase 2)
    |
    Zejula (niraparib)
    1m
    Radiation Therapy (RT) and Chemotherapy for the Treatment of Pancreatic Cancer with Homologous Recombination Deficiency That Has Spread to the Liver (clinicaltrials.gov)
    P1, N=1, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Nov 2024 | Trial primary completion date: Dec 2025 --> Nov 2024
    Trial completion • Trial completion date • Trial primary completion date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • BAP1 (BRCA1 Associated Protein 1) • 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) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • ABRAXAS1 (Abraxas 1 BRCA1 A Complex Subunit 2) • FANCC (FA Complementation Group C)
    |
    BRCA1 mutation • PALB2 mutation
    |
    MSK-IMPACT
    |
    cisplatin • gemcitabine
    1m
    Prospective germline sequencing of patients with gliomas, glioneuronal or neuronal tumors (SNO 2024)
    Clinical germline sequencing identifies a germline mutation in a high proportion of patients with CNS tumors. Biallelic inactivation was most commonly identified in tumors from patients with germline TP53 or NF1 mutations and were less common in patients with a germline MMR alteration.
    Clinical • BRCA Biomarker
    |
    TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NF1 (Neurofibromin 1) • CHEK2 (Checkpoint kinase 2) • MUTYH (MutY homolog)
    |
    TP53 mutation • NF1 mutation • CHEK2 mutation • IDH wild-type
    |
    MSK-IMPACT
    1m
    Radiation Therapy (RT) and Chemotherapy for the Treatment of Pancreatic Cancer With Homologous Recombination Deficiency That Has Spread to the Liver (clinicaltrials.gov)
    P1, N=1, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • BAP1 (BRCA1 Associated Protein 1) • 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) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • ABRAXAS1 (Abraxas 1 BRCA1 A Complex Subunit 2) • FANCC (FA Complementation Group C)
    |
    BRCA1 mutation • PALB2 mutation
    |
    MSK-IMPACT
    |
    cisplatin • gemcitabine
    2ms
    Genomic and Clinicopathologic Profiling of Breast Invasive Lobular Carcinoma in Patients with Germline Predisposition (SABCS 2024)
    Despite the similarities between ILCs arising in the germline and sporadic settings, significant differences in their clinicopathologic and genomic features were identified, such as a higher rate of HER2-positivity and an enrichment in somatic genetic alterations in ERBB2 and in chromatin remodeling genes. These findings highlight opportunities for treatment personalization in patients with ILC who have germline predisposition.
    Clinical • BRCA Biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ARID1A (AT-rich interaction domain 1A) • KMT2D (Lysine Methyltransferase 2D) • KMT2C (Lysine Methyltransferase 2C) • PMS2 (PMS1 protein homolog 2) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • KDM6A (Lysine Demethylase 6A) • MUTYH (MutY homolog) • KMT2B (Lysine Methyltransferase 2B) • LZTR1 (Leucine Zipper Like Transcription Regulator 1)
    |
    HER-2 positive • HER-2 negative
    |
    MSK-IMPACT
    2ms
    Clinical Outcomes and the 21-Gene Recurrence Score Assay in Early-Stage Breast Cancer Associated with CHEK2, ATM and PALB2 Germline Pathogenic Variants (SABCS 2024)
    Our data demonstrate that higher Oncotype RS, CHEK2 mutations, lymphatic and vascular invasion, and higher Ki67 levels were identified as predictors of poorer RFS. Conversely, older age (>50 years), adjuvant ET, and adjuvant XRT were associated with improved RFS. Importantly, the presence of ATM, CHEK2, or PALB2 mutations did not significantly impact OS.
    Clinical • Clinical data
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • ATM (ATM serine/threonine kinase) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2)
    |
    ER positive • HR positive • HER-2 negative • ATM mutation • PALB2 mutation • CHEK2 mutation • HR positive + HER-2 negative • PGR negative • HER-2 negative + ER positive
    |
    Oncotype DX Breast Recurrence Score®Test
    2ms
    Comprehensive characterization of the androgen receptor in male breast cancer (SABCS 2024)
    Our analysis suggests a strong association between AR expression and TP53 mutations, TMB-H, and PD-L1 positivity, immune cell infiltration, immune checkpoint and stem cell-related gene. Also, T cell inflamed and IFNy score were inversely related. Further exploration of specific alterations and immune-oncology markers associated with AR expression may help in clinical trial design for male patients with BC.
    Tumor mutational burden • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • AR (Androgen receptor) • IFNG (Interferon, gamma) • LAG3 (Lymphocyte Activating 3) • CHEK2 (Checkpoint kinase 2) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • CD34 (CD34 molecule) • KLF4 (Kruppel-like factor 4) • POU5F1 (POU Class 5 Homeobox 1) • ALDH2 (Aldehyde Dehydrogenase 2 Family Member) • FOXP3 (Forkhead Box P3)
    |
    TP53 mutation • TMB-H • TP53 wild-type • AR overexpression • AR expression • TP53 expression • FOXP3 expression
    |
    MI Tumor Seek™
    2ms
    Chidamide Combined with (+) -JQ-1 to Kill MLL-Rearrangement Acute Myeloid Leukemia Cells by Disrupting the DNA Damage Response Pathway (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi)
    Chidamide combined with (+)-JQ-1 can inhibit the proliferation of MLL-r AML cells, inhibit the initiation of protective self-repair of these leukemia cells by inhibiting the DNA damage response pathway, and ultimately increase the apoptosis of these cells, but non- MLL-r AML cells have no similar results.
    Journal • IO biomarker
    |
    BCL2 (B-cell CLL/lymphoma 2) • KMT2A (Lysine Methyltransferase 2A) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • CHEK1 (Checkpoint kinase 1) • BAX (BCL2-associated X protein) • CASP3 (Caspase 3) • BRD4 (Bromodomain Containing 4) • TP53BP1 (Tumor Protein P53 Binding Protein 1)
    |
    MLL rearrangement • MLL rearrangement • BCL2 expression • BAX expression
    |
    JQ-1 • Epidaza (chidamide)
    2ms
    Tumour-intrinsic PDL1 signals regulate the Chk2 DNA damage response in cancer cells and mediate resistance to Chk1 inhibitors. (PubMed, Mol Cancer)
    Our data challenge the prevailing surface PDL1 paradigm, elucidate important and previously unappreciated roles for tumour-intrinsic PDL1 in regulating the ATM/Chk2 DNA damage response axis and E3 ligase-mediated protein degradation, suggest tumour PDL1 as a biomarker for Chk1i efficacy, and support the rapid clinical potential of pharmacologic tumour PDL1 depletion to treat selected cancers.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    CHEK2 (Checkpoint kinase 2)
    |
    PD-L1 expression