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

    CHEK1 expression

    i
    Other names: CHEK1, CHK1, Checkpoint kinase 1
    Entrez ID:
    1111
    Related biomarkers:
    Expression
    Mutation
    Associations

    News

    Trials
    1m
    Cabozantinib and Pamiparib for the Treatment of Advanced of Refractory Solid Tumors (clinicaltrials.gov)
    P1, N=44, Recruiting, M.D. Anderson Cancer Center | Active, not recruiting --> Recruiting
    Enrollment open • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • CHEK2 (Checkpoint kinase 2) • RAD50 (RAD50 Double Strand Break Repair Protein) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • CHEK1 (Checkpoint kinase 1) • EMSY (EMSY Transcriptional Repressor BRCA2 Interacting)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CHEK2 mutation • RAD50 mutation • CHEK1 mutation • CHEK1 expression
    |
    Cabometyx (cabozantinib tablet) • Partruvix (pamiparib)
    2ms
    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 2025 --> Mar 2026 | Trial primary completion date: Mar 2024 --> Mar 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    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)
    |
    BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • RAD54L mutation • RAD51 mutation • CHEK1 expression
    |
    Lynparza (olaparib)
    3ms
    Cabozantinib and Pamiparib for the Treatment of Advanced of Refractory Solid Tumors (clinicaltrials.gov)
    P1, N=44, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • CHEK2 (Checkpoint kinase 2) • RAD50 (RAD50 Double Strand Break Repair Protein) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • CHEK1 (Checkpoint kinase 1) • EMSY (EMSY Transcriptional Repressor BRCA2 Interacting)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CHEK2 mutation • RAD50 mutation • CHEK1 mutation • CHEK1 expression
    |
    Cabometyx (cabozantinib tablet) • Partruvix (pamiparib)
    4ms
    Histologic patterns in prostatic adenocarcinoma are not predictive of mutations in the homologous recombination repair pathway. (PubMed, Hum Pathol)
    Tumors with >20  % or >30  % histologic patterns by volume also demonstrated no significant association with mutational status. This study suggests that histopathologic examination alone is insufficient to distinguish prostate cancer with germline or somatic mutations in HRR pathway genes, highlighting the continuing importance of ancillary molecular diagnostics in guiding therapy selection for prostate cancer patients who may benefit from PARP inhibitors.
    Journal • BRCA Biomarker • PARP Biomarker
    |
    HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • 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)) • EMSY (EMSY Transcriptional Repressor BRCA2 Interacting) • ABRAXAS1 (Abraxas 1 BRCA1 A Complex Subunit 2)
    |
    BRCA2 mutation • BRCA1 mutation • PALB2 mutation • CHEK1 expression
    5ms
    Real-world homologous recombination repair mutation (HRRm) testing patterns in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with olaparib in the United States. (ASCO-GU 2024)
    Pts with confirmed mCRPC diagnosis, age ≥21 years, treated with olaparib monotherapy after exposure to abiraterone or enzalutamide, and with positive HRRm status were included. This real-world analysis highlights the need for earlier HRRm testing in pts with mCRPC to allow for optimal timing of novel treatment options that have shown efficacy in a biomarker-selected population. Most pts in this study were tested and diagnosed with HRRm many months after mCRPC diagnosis, at which point they had high levels of bone metastasis, multiple sites of distant metastases, and opioid use at the initiation of olaparib treatment. HRR testing in pts before or at the time of mCRPC would allow for olaparib therapy earlier in the disease course.
    Real-world evidence • Clinical • PARP Biomarker • BRCA Biomarker • Real-world • Metastases
    |
    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) • BRCA (Breast cancer early onset) • 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)
    |
    BRCA1 mutation • ATM mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • CHEK1 expression
    |
    Lynparza (olaparib) • Xtandi (enzalutamide capsule) • abiraterone acetate
    5ms
    Efficacy of olaparib (O) plus abiraterone (A) versus placebo (P) plus A in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) with single homologous recombination repair gene mutations (HRRm) in the PROpel trial. (ASCO-GU 2024)
    BRCA2, ATM and CDK12 were the most prevalent single gene mutations and clinical benefit was observed with O + A. Other single gene mutations were rare, limiting interpretation. The greatest treatment benefit was observed in pts with BRCA mutations. Clinical trial information: NCT03732820.NR, not reached; BRIP1, RAD51B, RAD51D n=1; CHEK1, RAD51C n=0.
    Clinical • PARP Biomarker • BRCA Biomarker • Metastases
    |
    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) • BRCA (Breast cancer early onset) • 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)
    |
    ATM mutation • CDK12 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BRCA mutation • CHEK1 mutation • BRCA2 mutation + ATM mutation • CHEK1 expression
    |
    FoundationOne® CDx • FoundationOne® Liquid CDx
    |
    Lynparza (olaparib) • abiraterone acetate
    6ms
    Leveraging synthetic lethality to uncover potential therapeutic target in gastric cancer. (PubMed, Cancer Gene Ther)
    Since trastuzumab was approved in 2012 for the first-line treatment of gastric cancer (GC), no significant advancement in GC targeted therapies has occurred...Meanwhile, in vitro experimental validation of two novel synthetic lethal pairs TP53-AURKB and ARID1A-EP300 further proved the universality and reliability of GSSL. Collectively, GSSL has been shown to be a reliable and feasible method for comprehensive analysis of inferring synthetic lethal interactions of GC, which may offer novel insight into the precision medicine and individualized treatment of GC.
    Journal • Synthetic lethality
    |
    TP53 (Tumor protein P53) • ARID1A (AT-rich interaction domain 1A) • EP300 (E1A binding protein p300) • AURKB (Aurora Kinase B)
    |
    TP53 mutation • CHEK1 expression
    |
    Herceptin (trastuzumab)
    6ms
    Whole Exome Sequencing reveals clinically important pathogenic mutations in DNA repair genes across lung cancer patients. (PubMed, Am J Cancer Res)
    The observed pathogenic mutations in BRCA1, BRCA2, ERCC6, CHEK1, MUTYH, and RAD51D, coupled with their down-regulation and hypermethylation, suggest a potential convergence of genetic and epigenetic factors driving genomic instability in lung cancer cells. These findings contribute to our understanding of lung cancer susceptibility and highlight potential avenues for targeted therapeutic interventions in Pakistani lung cancer patients.
    Journal • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51 (RAD51 Homolog A) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • MUTYH (MutY homolog) • ERCC6 (Excision repair cross-complementation group 6)
    |
    BRCA2 mutation • BRCA1 mutation • RAD51D mutation • CHEK1 mutation • RAD51 mutation • CHEK1 expression
    6ms
    The role of DNA repair genes mutational status in prostate cancer treatment with androgen signaling blockade (EMUC 2023)
    Probably, the data obtained on the worst efficacy of enzalutamide after docetaxel in patients with mutations in  HRR genes can be attributed to the biological features of the influence of therapy methods on the course of the disease. In clinical practice, it is advisable to take into account the fact of the influence of previous treatment on the effectiveness of antiandrogenic therapy in choosing the sequence of treatment methods.
    BRCA Biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • 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) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51B mutation • CHEK1 mutation • RAD54L mutation • CHEK1 expression
    |
    docetaxel • Xtandi (enzalutamide capsule)
    8ms
    Olaparib in Men With High-Risk Biochemically-Recurrent Prostate Cancer Following Radical Prostatectomy, With Integrated Biomarker Analysis (clinicaltrials.gov)
    P2, N=50, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Recruiting --> Active, not recruiting | Trial primary completion date: Sep 2023 --> May 2023
    Enrollment closed • Trial primary completion date
    |
    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) • 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) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
    |
    BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • CHEK1 expression
    |
    Lynparza (olaparib)
    8ms
    Targeting splicing factor mutations in Myelodysplastic Neoplasms (MDS) (DGHO 2023)
    Analysis of differentially expressed genes (DEGs) between SF-mutant vs wild type samples in Beat AML and GSE146172 cohorts identified 801 and 262 DEGs respectively (p<0.01). There was an overlap of 68 common DEGs between two cohorts. Overall, higher drug prediction scores were obtained for GSE146172 cohort.
    PARP Biomarker
    |
    SF3B1 (Splicing Factor 3b Subunit 1) • SRSF2 (Serine and arginine rich splicing factor 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CD34 (CD34 molecule) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • CHEK1 (Checkpoint kinase 1) • CDK2 (Cyclin-dependent kinase 2) • PARP2 (Poly(ADP-Ribose) Polymerase 2)
    |
    SF3B1 mutation • SRSF2 mutation • U2AF1 mutation • CHEK1 expression
    8ms
    The Genomic Landscape of Colorectal Cancer in the Saudi Arabian Population Using a Comprehensive Genomic Panel. (PubMed, Diagnostics (Basel))
    These results may help optimize personalized therapy when drugs specific to a patient's mutation profile have already been developed.
    Journal • BRCA Biomarker
    |
    BRCA2 (Breast cancer 2, early onset) • PMS2 (PMS1 protein homolog 2) • APC (APC Regulator Of WNT Signaling Pathway) • CHEK1 (Checkpoint kinase 1) • MYCL (MYCL Proto-Oncogene BHLH Transcription Factor)
    |
    ATM mutation • PMS2 mutation • CHEK1 mutation • CHEK1 expression
    8ms
    Olaparib in Men With High-Risk Biochemically-Recurrent Prostate Cancer Following Radical Prostatectomy, With Integrated Biomarker Analysis (clinicaltrials.gov)
    P2, N=50, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Feb 2024 --> Feb 2025
    Trial completion date
    |
    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) • 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) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
    |
    BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • CHEK1 expression
    |
    Lynparza (olaparib)
    8ms
    Ovarian High-grade Serous Carcinoma with Transitional-like (SET) Morphology: A Homologous Recombination-deficient Tumor. (PubMed, Hum Pathol)
    "Our results show that the majority of HGSCs with SET features are homologous recombination deficient tumors independently of the BRCA status and highlight the importance of the homologous recombination repair tumor testing especially in BRCA wild-type tumors. Recognition of transitional cell variant of HGSCs may help to identify patients most likely to benefit from PARP inhibitors."
    Journal
    |
    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) • BRCA (Breast cancer early onset) • 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)
    |
    BRCA2 mutation • BRCA1 mutation • HRD • ATM mutation • PALB2 mutation • BRCA wild-type • CDK12 mutation • BRIP1 mutation • HRD + BRCA1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • RAD54L mutation • CHEK1 expression
    |
    Myriad myChoice® CDx Plus • SOPHiA DDM HRD Solution
    10ms
    Application value of whole exon sequencing and immune related indicators in the precision treatment of oral squamous cell carcinoma (PubMed, Beijing Da Xue Xue Bao Yi Xue Ban)
    The present results do not support the wide application and promotion of genetic testing and immune related indexes in OSCC.
    Journal • Tumor mutational burden • IO biomarker
    |
    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • CHEK1 (Checkpoint kinase 1) • HLA-B (Major Histocompatibility Complex, Class I, B)
    |
    TP53 mutation • CHEK1 mutation • CHEK1 expression
    10ms
    HRD status of patients with early stage non-small cell lung cancer (ESMO 2023)
    Preliminary functional experiments in HRP (HR proficient, n=5) and HRD (n=4) PDX and organoids (n=3 and n=3 for HRD and HRP respectively) indicate that HRD tumors present low RAD51 foci count (p=0.03 after damage induction) and favorable response to Olaparib and CDDP. Conclusions These data suggest that homologous recombination may be deficient in a substantial proportion of early-stage NSCLC patients, supporting the potential use of PARPi in HRD patients in the adjuvant or maintenance setting.
    Clinical • PARP Biomarker • BRCA Biomarker
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • RAD50 (RAD50 Double Strand Break Repair Protein) • CHEK1 (Checkpoint kinase 1)
    |
    BRCA2 mutation • BRCA1 mutation • HRD • ATM mutation • PALB2 mutation • CHEK2 mutation • HRD + BRCA1 mutation • RAD50 mutation • CHEK1 mutation • CHEK1 expression
    |
    AmoyDx® HRD Focus Panel
    |
    Lynparza (olaparib)
    10ms
    Homologous recombination repair (HRR) gene mutation: A novel biomarker for precision genomics testing in advanced lung cancer (ESMO 2023)
    Table: 1429P Conclusions The HRR gene mutation in advanced lung cancer was independent of the predictors for immunotherapy response (TMB, MSI and PD-L1 biomarkers). Further clinical trials are needed to assess the efficacy of combining poly ADP ribose polymerase (PARP) inhibitors with immunotherapy in the future.
    Tumor mutational burden • PD(L)-1 Biomarker • PARP Biomarker • BRCA Biomarker • IO biomarker • Metastases
    |
    TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • ARID1A (AT-rich interaction domain 1A) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
    |
    BRCA2 mutation • ATM mutation • ARID1A mutation • CDK12 mutation • BRIP1 mutation • FANCA mutation • RAD51B mutation • BARD1 mutation • BRCA mutation • CHEK1 mutation • CHEK1 expression
    |
    FoundationOne® CDx
    10ms
    Clinical significance of DNA damage response mutations in early stage NSCLC (ESMO 2023)
    Deleterious mutations in ATM, BRCA1/2, CHEK1, BARD1 and BRIP1 were independent prognostic indicators of significantly longer disease-free survival. Conclusions Deleterious mutations of these six genes were common in early-stage NSCLC and may serve as prognostic biomarkers.
    Clinical • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CD8 (cluster of differentiation 8) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1)
    |
    PD-L1 expression • BRCA2 mutation • BRCA1 mutation • ATM mutation • BRIP1 mutation • CD8 positive • BARD1 mutation • CHEK1 mutation • CHEK1 expression
    10ms
    LP-184, a Tumor Site Activated Small Molecule Acylfulvene, Is Effective Preclinically in Subsets of Lung Cancer (IASLC-WCLC 2023)
    H460 KEAP1/STK11 mutant cell line derived xenograft model was used to demonstrate the anti-tumor activity of LP-184. LP-184 displayed strong nanomolar potency in 7 day ex vivo treatment in a panel of patient derived lung cancer models carrying ATM, BRCA1 or CHEK1 mutations with IC50s in the range of 30 - 200 nM, which turned out to be 12-350 times superior to that of Olaparib across the same models. LP-184 is highly effective in selected molecular subsets of lung cancer in proof-of-concept ex vivo and in vivo studies, supporting its clinical development in small cell and non-small cell lung cancers. IND-enabling repeat dose GLP toxicology studies of LP-184 show it to be well tolerated in rats and dogs. A first-in-human dose escalation Phase 1A trial with LP-184 is expected to enroll all advanced solid tumors including lung cancers.
    Preclinical • BRCA Biomarker • PARP Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • STK11 (Serine/threonine kinase 11) • HRD (Homologous Recombination Deficiency) • KEAP1 (Kelch Like ECH Associated Protein 1) • CHEK1 (Checkpoint kinase 1) • PTGR1 (Prostaglandin Reductase 1) • RNF168 (Ring Finger Protein 168)
    |
    HRD • STK11 mutation • KEAP1 mutation • CHEK1 mutation • KEAP1 expression • PTGR1 expression • CHEK1 expression
    |
    Lynparza (olaparib) • hydroxyureamethylacylfulvene (STAR-001)
    10ms
    HRR Gene Mutations- A New Biomarker for Precision Genomics Based Testing in Metastatic Lung Cancer (IASLC-WCLC 2023)
    The emphasis on precision genomics-based targeted therapy in metastatic lung cancer is evolving rapidly and the addition of new HRR genes-based biomarker testing in lung cancer promotes opportunity for further clinical trials to assess the efficacy of combining PARP inhibitors with Immunotherapy in the future.
    Tumor mutational burden • PD(L)-1 Biomarker • PARP Biomarker • MSi-H Biomarker • BRCA Biomarker • IO biomarker • Metastases
    |
    PD-L1 (Programmed death ligand 1) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • ARID1A (AT-rich interaction domain 1A) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • 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) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • IL1R1 (Interleukin 1 receptor, type I) • PPP2R1A (Protein Phosphatase 2 Scaffold Subunit Aalpha)
    |
    PD-L1 expression • BRCA2 mutation • BRCA1 mutation • MSI-H/dMMR • ATM mutation • ARID1A mutation • PD-L1 negative • PALB2 mutation • CDK12 mutation • CHEK2 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • BRCA mutation • CHEK1 mutation • FANCG mutation • RAD51 mutation • CHEK1 expression
    |
    FoundationOne® CDx
    11ms
    The Genomic Landscape of Colorectal Cancer in the Saudi Arabian Population (AMP Europe 2023)
    In conclusion, we present a mutational landscape of actionable genes in CRC for the SA population in patients without a familial history of CRC. Additionally, we address the clinical relevance of low variant allele frequency variants. A comprehensive analysis of population-specific molecular markers for CRC can provide insights into the disease progression, with an aim of optimizing individualized therapeutic options and treatment regimens in the management of CRC in the SA population.
    Clinical • BRCA Biomarker
    |
    BRCA2 (Breast cancer 2, early onset) • PMS2 (PMS1 protein homolog 2) • CHEK1 (Checkpoint kinase 1) • MYCL (MYCL Proto-Oncogene BHLH Transcription Factor)
    |
    ATM mutation • PMS2 mutation • CHEK1 mutation • CHEK1 expression
    |
    Oncomine™ Comprehensive Assay v3M
    1year
    The application of a multigene NGS assay in homologous recombination deficiency tracking. (ASCO 2023)
    A high rate of HR mutations was detected in ovarian, breast and prostate which is consistent with the PARPi approval in these tumor types. The presence of BRCA1/2 mutations was highly associated with increased LOH value whereas it did not correlate to other HR mutations. Additionally, the pancancer presence of HR gene alterations indicates that the use of such genes as biomarkers of platinum and PARPi treatments should be evaluated in a wider range of tumor types.
    Tumor mutational burden • PARP Biomarker • BRCA Biomarker • IO biomarker • Next-generation sequencing
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • HRD (Homologous Recombination Deficiency) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog 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)) • WRN (WRN RecQ Like Helicase)
    |
    TP53 mutation • KRAS mutation • BRCA2 mutation • BRCA1 mutation • HRD • ATM mutation • ARID1A mutation • PALB2 mutation • BAP1 mutation • BRIP1 mutation • RAD50 mutation • BARD1 mutation • BLM mutation • MRE11A mutation • NBN mutation • CHEK1 expression
    |
    OncoScan™ CNV Assay
    1year
    A phase II study of olaparib (AZD2281) in patients (Pts) with metastatic/advanced urothelial carcinoma and other genitourinary (GU) tumors with DNA-repair defects. (ASCO 2023)
    This is an ECTCN network clinical trial and is open to enrollment. Clinical trial information: NCT03375307.
    P2 data • Clinical • Tumor mutational burden • PARP Biomarker • BRCA Biomarker • Metastases
    |
    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • ABL1 (ABL proto-oncogene 1) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • NPM1 (Nucleophosmin 1) • CCND1 (Cyclin D1) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • ATRX (ATRX Chromatin Remodeler) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • RAD51 (RAD51 Homolog A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • POLD1 (DNA Polymerase Delta 1) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • MUTYH (MutY homolog) • BRD4 (Bromodomain Containing 4) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon) • FANCC (FA Complementation Group C)
    |
    TMB-H • PALB2 mutation • CHEK2 mutation • BRIP1 mutation • BARD1 mutation • CHEK1 mutation • FANCG mutation • CHEK1 expression
    |
    FoundationOne® CDx
    |
    Lynparza (olaparib)
    1year
    HRD signature and HRD genomic landscape of tumors from 896 patients with early-stage breast cancer (BC). (ASCO 2023)
    PARP inhibitors (olaparib, talazoparib) are FDA-approved therapies that are toxic to tumors with HRR deficiency (HRD) and are recommended as adjuvant therapy in high-risk germline BRCA (gBRCA) positive BC. In this study, HR+/HER2- group was the most common early BC subtype, followed by HR-/HER2-, HR+/HER2+, and HR-/HER2+. This distribution is similar to the SEER study, and closely reflects that of the general population. We observed the expected high rates of HRDsig+ in early-stage BC pts with g/sBRCA or gPALB2 mutations where clinical trial data already support the use of PARP inhibitors for early and advanced disease.
    Clinical • PARP Biomarker • BRCA Biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • 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) • BRCA (Breast cancer early onset) • 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)
    |
    BRCA2 mutation • BRCA1 mutation • HER-2 negative • PALB2 mutation • RAD51C mutation • RAD51D mutation • BRCA mutation • HRD signature • CHEK1 expression
    |
    FoundationOne® CDx
    |
    Lynparza (olaparib) • Talzenna (talazoparib)
    1year
    Targeting CLDN6 in germ cell tumors by an antibody-drug-conjugate and studying therapy resistance of yolk-sac tumors to identify and screen specific therapeutic options. (PubMed, Mol Med)
    In summary, this study offers a novel CLDN6-ADC to target GCT. Additionally, this study presents novel pharmacological inhibitors blocking FGF, VGF, PDGF, mTOR, CHEK1, AURKA, or PARP signaling for the treatment of (refractory) YST patients. Finally, this study shed light on the mechanisms of therapy resistance in YST.
    Journal • PARP Biomarker
    |
    CLDN6 (Claudin 6) • AURKA (Aurora kinase A) • ANXA5 (Annexin A5)
    |
    CHEK1 expression
    |
    cisplatin
    1year
    The Prevalence of CHEK1 and CHEK2 Mutations in Prostate Cancer: a Retrospective Cohort Study. (PubMed, Med Arch)
    No association was found in this study between CHEK1 mutations and the development of PCa. Further studies are needed with larger cohorts along with a screening of more exons in order to shed more light on the frequency of CHEK2 gene mutations and their role in the development of PCa in Jordan.
    Retrospective data • Journal
    |
    CHEK2 (Checkpoint kinase 2) • CHEK1 (Checkpoint kinase 1)
    |
    CHEK2 mutation • CHEK1 mutation • CHEK1 expression
    1year
    LP-184, an acylfulvene class small molecule therapeutic, is synthetically lethal in DNA damage repair deficient cancers (AACR 2023)
    LP-184 treatment resulted in complete tumor regression (107-141% TGI) in 10/10 HR deficient triple negative breast cancer PDX models of which 7/10 were resistant Olaparib/ Niraparib and to Doxorubicin/ Cyclophosphamide. Unlike PARPi, LP-184 has striking activity in both NERD as well as HRD cancers. These strong data have prompted the development of a soon to be launched clinical trial to translate the broad preclinical anticancer activity of LP-184 in solid tumors with HR/NER pathway defects, such as pancreatic, prostate, ovarian and breast cancers.
    BRCA Biomarker • PARP Biomarker • Synthetic lethality
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • ERCC1 (Excision repair cross-complementation group 1) • ERCC2 (Excision repair cross-complementation group 2) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • ATR (Ataxia telangiectasia and Rad3-related protein) • CHEK1 (Checkpoint kinase 1) • PTGR1 (Prostaglandin Reductase 1)
    |
    BRCA2 mutation • BRCA1 mutation • HRD • ATM mutation • PALB2 mutation • HRD + BRCA1 mutation • FANCA mutation • CHEK1 mutation • PTGR1 expression • RAD51 mutation • CHEK1 expression
    |
    Lynparza (olaparib) • doxorubicin hydrochloride • Zejula (niraparib) • cyclophosphamide • hydroxyureamethylacylfulvene (STAR-001)
    1year
    Pan-cancer proteogenomics expands the landscape of therapeutic targets (AACR 2023)
    Based on tumor proteogenomic data and cell line CRISPR-Cas9 screen data, we identified synthetic lethality for difficult to target tumor suppressor losses, revealing TP53 mutations as a candidate biomarker to select breast cancer patients for CHEK1 inhibition, and endometrial cancer patients for treatment with doxorubicin... We generate a comprehensive resource of protein and peptide targets that covers multiple therapeutic modalities. This unique resource will pave the way for repurposing of currently available drugs and developing new drugs for cancer treatment.
    IO Companion diagnostic • IO biomarker • Pan tumor
    |
    TP53 (Tumor protein P53) • HLA-A (Major Histocompatibility Complex, Class I, A) • CHEK1 (Checkpoint kinase 1) • PTPN1 (Protein Tyrosine Phosphatase Non-Receptor Type 1)
    |
    TP53 mutation • HLA-A*02 • CHEK1 mutation • CHEK1 expression
    |
    doxorubicin hydrochloride
    1year
    The development of homologous recombination repair deficiency (HRD) score methodology using WES data and its application in patient-derived xenograft models (AACR 2023)
    Sixteen models found to carry HRR mutations, with ATM and BRCA1 mutations being the most common ones, being found in 9 and 5 of 25 models, respectively. Although HRRm positive (HRRm+) models have higher HRD score for both Myriad HRD score and HRD score generated with CNVkit/scarHRD approach, the association between HRR (HRRm+/HRRm-) and Myriad HRD (HRD+/HRD- defined by HRD threshold of 42) is not statistically significant (Fisher’s exact test p value = 0.1998, odds ratio=3.5), likely due to small cohort sizes.These results suggest that combination of CNVkit and scarHRD for HRD score calculation may be an alternative approach for HRD identification in preclinical PDX models.
    Preclinical • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • 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) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L)
    |
    BRCA1 mutation • HRD • ATM mutation • RAD51 mutation • CHEK1 expression • High HRD score
    |
    Myriad myChoice® CDx
    1year
    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 2024 --> Mar 2025 | Trial primary completion date: Mar 2023 --> Mar 2024
    Trial completion date • Trial primary completion date • Metastases
    |
    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)
    |
    BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • RAD54L mutation • RAD51 mutation • CHEK1 expression
    |
    Lynparza (olaparib)
    over1year
    Profiling of the genetic features of Chinese patients with gastric cancer with HRD germline mutations in a large-scale retrospective study. (PubMed, J Med Genet)
    Our data suggest that carrying both HRD and MMR gene LoF germline mutations may cause early-onset GC. Germline mutations in the HRD gene should be of concern in the study of hereditary GC.
    Retrospective data • Journal • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK1 (Checkpoint kinase 1) • FANCL (FA Complementation Group L)
    |
    BRCA2 mutation • BRCA1 mutation • HRD • ATM mutation • PALB2 mutation • CHEK2 mutation • BRIP1 mutation • HRD + BRCA1 mutation • FANCA mutation • CHEK1 mutation • CHEK1 expression
    over1year
    Are Histological Patterns of Prostate Carcinoma Predictive of Homologous Recombination Deficiency Gene Mutations? (USCAP 2023)
    In this study histological patterns were not predictive of HRD gene mutations. A marginal increase of neuroendocrine morphology and high-volume cribriform patterns were seen in BRCA1/2 and non- BRCA1/2 HRD mutated prostate carcinomas respectively. This data suggests that histopathologic examination alone is insufficient to distinguish BRCA1/2 and HRD gene mutated prostate cancers, further highlighting the importance of ancillary molecular diagnostics in therapy selection for those who may benefit from PARP inhibitors.
    BRCA Biomarker • PARP Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • 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) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • EMSY (EMSY Transcriptional Repressor BRCA2 Interacting) • ABRAXAS1 (Abraxas 1 BRCA1 A Complex Subunit 2)
    |
    BRCA2 mutation • BRCA1 mutation • HRD • ATM mutation • PTEN mutation • PALB2 mutation • CHEK2 mutation • BRIP1 mutation • HRD + BRCA1 mutation • RAD51C mutation • RAD51D mutation • BARD1 mutation • MRE11A mutation • NBN mutation • CHEK1 expression
    over1year
    Analysis of the frequency of occurrence of mutations in repair genes in patients with prostate cancer in the Republic of Bashkortostan (EMUC 2022)
    The results of the research showed the territorial features of the frequency of occurrence of germline and somatic mutations in the Republic of Bashkortostan. This research allowed to determine the tactics of treatment among patients with prostate cancer.
    Clinical • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset) • RAD51B (RAD51 Paralog B) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54)
    |
    BRCA mutation • CHEK1 expression
    over1year
    Olaparib in Men With High-Risk Biochemically-Recurrent Prostate Cancer Following Radical Prostatectomy, With Integrated Biomarker Analysis (clinicaltrials.gov)
    P2, N=50, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Feb 2023 --> Feb 2024 | Trial primary completion date: Sep 2022 --> Sep 2023
    Trial completion date • Trial primary completion date
    |
    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) • 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) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
    |
    BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • CHEK1 expression
    |
    Lynparza (olaparib)
    over1year
    The Study of Olaparib Combined With Abiraterone and Prednisone in mHSPC Patients With HRR Gene Mutation (clinicaltrials.gov)
    P2, N=30, Recruiting, Hongqian Guo | Not yet recruiting --> Recruiting
    Enrollment open
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • 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)
    |
    PALB2 mutation • CDK12 mutation • ATRX mutation • CHEK2 mutation • BRIP1 mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • RAD54L mutation • RAD51 mutation • CHEK1 expression
    |
    Lynparza (olaparib) • abiraterone acetate • prednisone
    over1year
    A prospective phase II study to investigate the efficacy and safety of olaparib plus abiraterone and prednisone combination therapy in mHSPC patients with HRR gene mutation (ESMO Asia 2022)
    1 of planned 30 patients have been enrolled until May. 2022.
    Clinical • P2 data • Combination therapy • BRCA Biomarker • PARP Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • 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)
    |
    BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • ATRX mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • RAD54L mutation • RAD51 mutation • CHEK1 expression
    |
    Lynparza (olaparib) • abiraterone acetate • prednisone
    almost2years
    The Prevalence of CHEK 1 and CHEK 2 mutations in prostate cancer in Jordan population: a retrospective cohort study (ECP 2022)
    We found, and in line with previous studies, lack of association between CHEK1 mutations and PCa development. The presence of 1.4% of mutation in CHEK2 in our results supported the possible role of genetic variants in this gene and the develop-ment of PCa. Further studies are needed with larger cohorts to shed more light on these findings and to reveal the genetic predisposi-tion of the CHEK2 gene in the development of PCa in Jordan and perform screening of more exons.
    Retrospective data
    |
    CHEK2 (Checkpoint kinase 2) • CHEK1 (Checkpoint kinase 1)
    |
    CHEK2 mutation • CHEK1 mutation • CHEK1 expression
    almost2years
    Concurrent loss of MLH1, PMS2 and MSH6 immunoexpression in gastrointestinal cancer indicating a widespread dysregulation in DNA reparation processes (ECP 2022)
    Our study suggests that the simultaneous loss of MLH1, PMS2 and MSH6 immunoexpression among diferent gastrointesti-nal cancers is associated with and potentially even based on more widespread alterations in DNA repair processes. Next-generation sequencing could reveal further mutations in additional DNA repair-related genes in the present cases. With the advent of drugs targeting DNA repair in clinical practice, especially PARP-inhibitors, and their potential indication extension for mutations other than BRCA1/2 such as PALB2 our results are of immediate clinical signifcance.
    BRCA Biomarker • PARP Biomarker
    |
    BRAF (B-raf proto-oncogene) • 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) • FANCA (FA Complementation Group A) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54)
    |
    BRAF V600E • BRCA2 mutation • BRCA1 mutation • BRAF V600 • ATM mutation • PALB2 mutation • FANCA mutation • RAD51D mutation • PMS2 mutation • BARD1 mutation • CHEK1 mutation • RAD54L mutation • CHEK1 expression • MSH6 expression
    almost2years
    Precision oncology and tumor mutational burden (TMB) in Merkel cell carcinoma (MCC): An analysis of the AACR Project Genie real-world database (ESMO 2022)
    Conclusions While most targetable mutations in MCC were likely passenger alterations in relation to tumor mutational status, there is a subset of MCC which have actionable alterations. These alterations support enrollment or treatment of MCC with targeted therapies.
    Clinical • Real-world evidence • Tumor Mutational Burden • BRCA Biomarker • IO biomarker
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRAS (Harvey rat sarcoma viral oncogene homolog) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • PTCH1 (Patched 1) • CHEK2 (Checkpoint kinase 2) • TSC1 (TSC complex subunit 1) • CHEK1 (Checkpoint kinase 1)
    |
    TMB-H • TMB-L • PTCH1 mutation • CHEK1 expression
    almost2years
    CHANGEABLE: Combination of HX008 And Niraparib in GErm-line-mutAted Metastatic Breast Cancer (clinicaltrials.gov)
    P2, N=37, Recruiting, Fudan University | Not yet recruiting --> Recruiting | Trial completion date: Apr 2022 --> Dec 2022 | Trial primary completion date: Feb 2022 --> Nov 2022
    Enrollment open • Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • BAP1 (BRCA1 Associated Protein 1) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • 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)) • FANCF (FA complementation group F) • WRN (WRN RecQ Like Helicase) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCC (FA Complementation Group C)
    |
    HER-2 positive • BRCA2 mutation • BRCA1 mutation • HR positive • HER-2 negative • ATM mutation • PALB2 mutation • CDK12 mutation • BAP1 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • HR positive + HER-2 negative • RAD50 mutation • BARD1 mutation • BLM mutation • CHEK1 mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • CHEK1 expression
    |
    Herceptin (trastuzumab) • Zejula (niraparib) • Puyouheng (pucotenlimab)
    2years
    Concurrent BRAFV600E and BRCA Mutations in MSS Metastatic Colorectal Cancer: Prevalence and Case Series of mCRC patients with prolonged OS. (PubMed, Cancer Treat Res Commun)
    Co-existence of BRAF V600E/BRCA1/2 may represent a unique subset of advanced MSS CRC that may have a better prognosis and represent an opportunity to test novel targeted therapies. The elevated gLOH in these cases may also be a valuable biomarker for these pts. Larger prospective clinical validation trials in this subset is warranted.
    Journal • BRCA Biomarker • MSi-H Biomarker
    |
    BRAF (B-raf proto-oncogene) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • 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)
    |
    BRAF V600E • BRCA2 mutation • BRCA1 mutation • MSI-H/dMMR • BRAF V600 • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • BRCA mutation • RAD54L mutation • CHEK1 expression
    2years
    Genomic and immunologic profiles of concurrent RB1 and CDKN1A/p21(WAF1) truncating mutations (RW+) in bladder cancer. (ASCO 2022)
    Truncating WAF1 mutations are associated with sensitivity to cisplatin and are associated with truncating Rb mutations in bladder cancer (RW+)... Concurrent truncating mutation in RB1 and WAF1 (RW+) bladder carcinomas have fewer p53, ARID1A, and PIK3CA mutations but are enriched for E2F targets, G2/M checkpoint genes, FANCC/A, CHEK1, WEE1, CDC25A/C, PALB2 and BRCA1/2 and have a distinct immunological profile. The findings suggest therapeutic strategies for RW+ bladder cancers including Chk1/Wee1, PARP inhibitors, -/+ immunotherapy that may impact on clinical outcomes.
    PD(L)-1 Biomarker • PARP Biomarker • BRCA Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • 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) • FGFR3 (Fibroblast growth factor receptor 3) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • PALB2 (Partner and localizer of BRCA2) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • CDC25A (Cell Division Cycle 25A) • FANCC (FA Complementation Group C) • GNRP (Ras-Specific Guanine Nucleotide-Releasing Factor 1)
    |
    TP53 mutation • PIK3CA mutation • ARID1A mutation • PALB2 mutation • FGFR3 mutation • RB1 mutation • CHEK1 mutation • CHEK1 expression
    |
    MI Tumor Seek™
    |
    cisplatin