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    GENE:

    RAD51D (RAD51 paralog D)

    i
    2d
    Role of DNA methylation and non‑coding RNAs expression in pathogenesis, detection, prognosis, and therapy‑resistant ovarian carcinoma (Review). (PubMed, Mol Med Rep)
    The present review focused on the role of DNA methylation and non‑coding RNA expression in the development of ovarian carcinomas and their association with diagnosis, prognosis, and the resistance of cancer cells to radiotherapy and chemotherapy. The present review considered the transition from the DNA structure to the RNA expression in ovarian carcinoma.
    Review • Journal • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • MSH2 (MutS Homolog 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
    5d
    Germline variants analysis of Chinese breast cancer patients reveals numerous alterations in homologous recombination genes. (PubMed, Future Sci OA)
    All three patients with the pathogenic variant (p.Lys91fs) in RAD51D were diagnosed with triple-negative breast cancer. HR-gene testing in breast cancer could help to find new suspected pathogenic variants and increase the clinical benefit of multi-gene testing for breast cancer.
    Journal • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D)
    9d
    Genomic Signature for Initial Brain Metastasis Velocity (iBMV) in Non-Small-Cell Lung Cancer Patients: The Elusive Biomarker to Predict the Development of Brain Metastases? (PubMed, Cancers (Basel))
    Patients with a positive iBMV risk score were more likely to develop brain metastases. Validation of this signature could lead to a biomarker with the potential to guide treatment recommendations and surveillance schedules.
    Journal
    |
    BRAF (B-raf proto-oncogene) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • GNAQ (G Protein Subunit Alpha Q) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • CDK4 (Cyclin-dependent kinase 4) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • TSC1 (TSC complex subunit 1) • RAD51D (RAD51 paralog D) • ARAF (A-Raf Proto-Oncogene)
    12d
    CERTIS1: Study of AZD9574 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Advanced Solid Malignancies (clinicaltrials.gov)
    P1/2, N=490, Recruiting, AstraZeneca | Trial completion date: Aug 2026 --> Feb 2027 | Trial primary completion date: Aug 2026 --> Feb 2027
    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) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
    |
    HER-2 negative • PALB2 mutation • RAD51C mutation • RAD51D mutation
    |
    temozolomide • Enhertu (fam-trastuzumab deruxtecan-nxki) • Datroway (datopotamab deruxtecan) • AZD9574
    17d
    NCI10217: Testing the Combination of the Anti-cancer Drugs Copanlisib, Olaparib, and MEDI4736 (Durvalumab) in Patients With Advanced Solid Tumors With Selected Mutations (clinicaltrials.gov)
    P1, N=39, Active, not recruiting, National Cancer Institute (NCI) | N=108 --> 39 | Trial completion date: Dec 2024 --> Mar 2026 | Trial primary completion date: Dec 2024 --> Jul 2024
    Enrollment change • Trial completion date • Trial primary completion date
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • 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) • CD4 (CD4 Molecule) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))
    |
    PIK3CA mutation • PTEN mutation • PALB2 mutation • CDK12 mutation • BARD1 mutation
    |
    Lynparza (olaparib) • Imfinzi (durvalumab) • Aliqopa (copanlisib)
    18d
    Talazoparib and Palbociclib, Axitinib, or Crizotinib for the Treatment of Advanced or Metastatic Solid Tumors, TalaCom Trial (clinicaltrials.gov)
    P1, N=111, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Sep 2025 --> Dec 2027 | Trial primary completion date: Sep 2025 --> Dec 2027
    Trial completion date • Trial primary completion date
    |
    ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
    |
    MET amplification • MET expression • ALK translocation
    |
    Xalkori (crizotinib) • Ibrance (palbociclib) • Talzenna (talazoparib) • Inlyta (axitinib)
    19d
    D5330C00004: Ascending Doses of Ceralasertib in Combination With Chemotherapy and/or Novel Anti Cancer Agents (clinicaltrials.gov)
    P1/2, N=357, Active, not recruiting, AstraZeneca | Trial completion date: Mar 2025 --> Dec 2025 | Recruiting --> Active, not recruiting
    Enrollment closed • Trial completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
    |
    HER-2 negative • HRD • PALB2 mutation • RAD51C mutation • BRCA mutation
    |
    Lynparza (olaparib) • carboplatin • Imfinzi (durvalumab) • ceralasertib (AZD6738) • saruparib (AZD5305)
    25d
    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
    |
    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)
    |
    ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • RAD54L mutation
    |
    Lynparza (olaparib)
    25d
    Pathogenic germline variants in cancer predisposition genes in patients with multiple primary cancers in an Asian population and the role of extended panel genetic testing. (PubMed, ESMO Open)
    Patients with MPC were more likely to harbour a PGV. Extended testing improved PGV detection rates, particularly for less well-known cancer predisposition genes.
    Journal • BRCA Biomarker
    |
    TP53 (Tumor protein P53) • 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) • TET2 (Tet Methylcytosine Dioxygenase 2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • MBD4 (Methyl-CpG Binding Domain 4, DNA Glycosylase) • BARD1 (BRCA1 Associated RING Domain 1) • DDX41 (DEAD-Box Helicase 41) • FANCL (FA Complementation Group L) • CTNNA1 (Catenin Alpha 1) • RECQL4( RecQ Like Helicase 4) • SPINK1 (Serine peptidase inhibitor, kazal type 1) • CDKN1C (Cyclin Dependent Kinase Inhibitor 1C) • TNFRSF13B (TNF Receptor Superfamily Member 13B)
    28d
    Reduced reproductive potential in young healthy women with hereditary breast and/or ovarian cancer syndrome. (PubMed, Commun Med (Lond))
    A consistent trend for reduced reproductive potential in young, healthy women with HBOC syndrome is observed, particularly in BRCA1 P/LPV carriers. These findings need to be confirmed by larger studies including also women carrying P/LPV in other HBOC syndrome-related genes.
    Journal • BRCA Biomarker
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D)
    1m
    Pathogenic germline variants in Chinese pancreatic adenocarcinoma patients. (PubMed, Nat Commun)
    Using an integrative multi-omics and functional validation paradigm, we discover that deleterious variants of uncertain significance may compromise CFTR's tumor suppressor function, and demonstrate the clinical relevance by using patient derived organoids for drug screen. Our multifaceted approach not only deepens the knowledge of population differences in PAAD germline mutations but also unveils potential avenues for targeted therapeutic interventions.
    Journal • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ERCC2 (Excision repair cross-complementation group 2) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51D (RAD51 paralog D) • GNAS (GNAS Complex Locus)
    |
    ATM mutation • CHEK2 mutation • RAD51D mutation
    1m
    Reclassification of variants of uncertain significance by race, ethnicity, and ancestry for patients at risk for breast cancer. (PubMed, Front Oncol)
    This study allows for improved and more equitable genetic counseling. It may also provide more reassurance to those groups that may have a higher likelihood of VUS results.
    Journal • BRCA Biomarker
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • NF1 (Neurofibromin 1) • 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
    Prevalence of Constitutional Pathogenic Variant in a Cohort of 348 Patients With Multiple Primary Cancer Addressed in Oncogenetic Consultation. (PubMed, Mol Genet Genomic Med)
    Patients referred for oncogenetic testing with MPM are more likely to carry pathogenic variants in cancer predisposition genes than patients with a single primary cancer (p < 0.05), especially if the cancers are related to the same predisposition syndrome. If the cancers are unrelated, no statistical difference in comparison to the single-cancer population was observed. For these latter patients, we recommend using the specific criteria of each tumor to propose appropriate genetic testing.
    Journal • BRCA Biomarker
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • EPCAM (Epithelial cell adhesion molecule) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))
    1m
    Considerations for hereditary breast and ovarian cancer syndrome molecular diagnosis: experience from the clinical practice. (PubMed, Breast Cancer Res Treat)
    Testing cancer susceptibility genes using an agnostic strategy confers a diagnostic benefit for hereditary cancer syndromes compared to phenotype-driven test, without adding complexity to the study. The analysis of healthy individuals with a family history of HBOC detects pathogenic variants in a cost-efficient percentage of cases, resulting in a good alternative strategy when the index case is unavailable.
    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) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • 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)
    2ms
    Mutations in homologous recombination repair genes in patients with metastatic endometrial cancer: association with clinical characteristics and prognosis. (PubMed, J Gynecol Oncol)
    Somatic HRR mutations are detected in 11.8% of metastatic EC. Compared with noncarriers, HRR mutation carriers in metastatic EC have higher proportions of endometrioid carcinoma, POLEmut, and dMMR subtypes, and unique metastatic patterns. However, the prognoses are similar regardless of HRR status.
    Journal • BRCA Biomarker
    |
    TP53 (Tumor protein P53) • 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)
    |
    TP53 mutation • MSI-H/dMMR • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • BARD1 mutation
    2ms
    Exome sequencing identifies HELB as a novel susceptibility gene for non-mucinous, non-high-grade-serous epithelial ovarian cancer. (PubMed, Eur J Hum Genet)
    The other five genes were OR2T35, HELB, MYO1A and GABRP which were associated with non-high-grade serous ovarian cancer and MIGA1 which was associated with high-grade serous ovarian cancer. Further support for the association of HELB association comes from the observation that loss-of-function variants in HELB are associated with age at natural menopause and Mendelian randomisation analysis shows an association between genetically predicted age at natural menopause and endometrioid ovarian cancer, but not high-grade serous ovarian cancer.
    Journal • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • MSH6 (MutS homolog 6) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • GABRP (Gamma-Aminobutyric Acid Type A Receptor Subunit Pi)
    2ms
    Stand Up to Cancer: MAGENTA (Making Genetic Testing Accessible) (clinicaltrials.gov)
    P=N/A, N=5200, Suspended, M.D. Anderson Cancer Center | Trial completion date: Apr 2024 --> Apr 2026 | Recruiting --> Suspended | Trial primary completion date: Apr 2024 --> Apr 2026
    Trial completion date • Trial suspension • Trial primary completion date
    |
    ER (Estrogen receptor) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)
    |
    PALB2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • BARD1 mutation
    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
    |
    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)
    |
    CDKN2A deletion • BRIP1 mutation • RAD51C mutation • RAD51B mutation • BARD1 mutation • IDH wild-type
    |
    Keytruda (pembrolizumab) • Lynparza (olaparib) • temozolomide
    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
    |
    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
    |
    Lynparza (olaparib)
    2ms
    HRPCa-II: Evaluation of a Multimodal Strategy for Early Diagnosis of Men At High Genetic Risk of Prostate Cancer (clinicaltrials.gov)
    P=N/A, N=880, Not yet recruiting, Assistance Publique - Hôpitaux de Paris | Trial completion date: Dec 2029 --> Mar 2030 | Trial primary completion date: Dec 2029 --> Mar 2030
    Trial completion date • Trial primary completion date
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • HOXB13 (Homeobox B13)
    |
    PALB2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • BARD1 mutation
    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
    |
    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)
    3ms
    A Study of Olaparib and Pembrolizumab in People with Triple Negative Breast Cancer (TNBC) or Hormone Receptor-positive HER2-negative Breast Cancer (clinicaltrials.gov)
    P2, N=23, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
    |
    BRCA2 mutation • BRCA1 mutation • HR positive • HER-2 negative • PALB2 mutation • RAD51C mutation • RAD51D mutation • HR positive + HER-2 negative • RAD51 mutation • HER-2 negative + HR positive + BRCA mutation
    |
    Keytruda (pembrolizumab) • Lynparza (olaparib)
    3ms
    Niraparib and Dostarlimab for the Treatment of Germline or Somatic BRCA1/2 and PALB2 Mutated Metastatic Pancreatic Cancer (clinicaltrials.gov)
    P2, N=22, Active, not recruiting, Mayo Clinic | Trial completion date: Sep 2024 --> Jun 2025
    Trial completion date • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)
    |
    PD-L1 expression • PD-1 expression
    |
    Zejula (niraparib) • Jemperli (dostarlimab-gxly)
    3ms
    A portrait of germline pathogenic variants in high and moderate penetrance breast cancer genes in Brazil. (PubMed, Front Oncol)
    Deleterious BRCA1/2 variants vary according to age and BC subtype. Our study gives a broader understanding of BC risk genes and has opened doors to optimized testing and surveillance strategies in Brazil.
    Journal • BRCA Biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • NF1 (Neurofibromin 1) • 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)
    |
    ATM R337H
    3ms
    Pembrolizumab, Olaparib, Recurrent/Advanced Gastric and Gastro-esophageal Junction(GEJ) Cancer (clinicaltrials.gov)
    P1/2, N=71, Recruiting, Yonsei University | Not yet recruiting --> Recruiting | Trial completion date: May 2023 --> May 2025 | Trial primary completion date: Dec 2022 --> Dec 2024
    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) • HRD (Homologous Recombination Deficiency) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • 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) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
    |
    HER-2 positive • BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • CHEK1 expression
    |
    Keytruda (pembrolizumab) • Lynparza (olaparib) • paclitaxel
    3ms
    CERTIS1: Study of AZD9574 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Advanced Solid Malignancies (clinicaltrials.gov)
    P1/2, N=490, Recruiting, AstraZeneca | Trial completion date: Jan 2026 --> Aug 2026 | Trial primary completion date: Jan 2026 --> Aug 2026
    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) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
    |
    BRCA2 mutation • BRCA1 mutation • HER-2 negative • PALB2 mutation • RAD51C mutation • RAD51D mutation • RAD51 mutation
    |
    temozolomide • Enhertu (fam-trastuzumab deruxtecan-nxki) • Datroway (datopotamab deruxtecan) • AZD9574
    4ms
    Patterns of genomic instability in > 2000 patients with ovarian cancer across six clinical trials evaluating olaparib. (PubMed, Genome Med)
    These analyses provide valuable insight into patterns of genomic instability and potential drivers of HRD, besides BRCAm, in ovarian cancer and will help guide future research into the potential clinical effectiveness of anti-cancer treatments in ovarian cancer, including PARP inhibitors as well as other precision oncology agents.
    Journal • BRCA Biomarker • PARP Biomarker
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • CCNE1 (Cyclin E1) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
    |
    PIK3CA mutation • HRD • CCNE1 amplification • PIK3CA amplification • BRIP1 mutation • RAD51C mutation • RAD51D mutation
    |
    Lynparza (olaparib)
    4ms
    PRMT5-regulated splicing of DNA repair genes drives chemoresistance in breast cancer stem cells. (PubMed, Oncogene)
    Surprisingly, these skipped exons and retained intron events rarely lead to substantial gene expression repression, suggesting that PRMT5 inhibition predominantly results in nuclear detention of intron-containing transcripts and the production of non-canonical isoforms with compromised protein function. Since many genes within the same DDR pathway undergo deregulated splicing, this study thus reveals additional points of vulnerability and alternative combination drug strategies that could improve the therapeutic efficacy of PRMT5 inhibitors to promote BCSC eradication.
    Journal
    |
    RAD51D (RAD51 paralog D) • RAD17 (RAD17 Checkpoint Clamp Loader Component) • RUVBL1 (RuvB Like AAA ATPase 1) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)
    4ms
    Comprehensive Clinical Genetics, Molecular and Pathological Evaluation Efficiently Assist Diagnostics and Therapy Selection in Breast Cancer Patients with Hereditary Genetic Background. (PubMed, Int J Mol Sci)
    Further immunohistochemistry analysis of breast tumour tissues helped clarify the causative role of these variants. Comprehensive clinical and molecular genetic evaluation is beneficial for the diagnosis and management of patients with P/LP variants in hereditary tumour-predisposing genes and can serve as a basis for effective therapy selection, such as PARP inhibitors or immunotherapy.
    Retrospective data • Journal • BRCA Biomarker • PARP Biomarker • IO biomarker
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ATM (ATM serine/threonine kinase) • STK11 (Serine/threonine kinase 11) • NF1 (Neurofibromin 1) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)
    4ms
    Response to Carboplatin and Paclitaxel in the treatment of hereditary breast ovarian cancer syndrome (HBOC): a case report. (PubMed, J Pak Med Assoc)
    This dynamic treatment not only led to nearly complete remission of high-grade ovarian serous cancer but also triggered regression in grade-2 invasive ductal breast cancer after just a few rounds of chemotherapy. Consequently, what started as palliative care evolved into a curative triumph.
    Journal • BRCA Biomarker
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    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1)
    |
    TP53 mutation • BRCA2 mutation • BRCA1 mutation • PALB2 mutation • CHEK1 mutation • CHEK1 expression
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    carboplatin • paclitaxel
    4ms
    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
    |
    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
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    Talzenna (talazoparib)
    4ms
    Investigating the effects of the ARG258HIS mutation on RAD51C in inherited Fanconi Anemia and cancer disease. (PubMed, J Biomol Struct Dyn)
    These simulations highlighted alterations in conformational dynamics, the Free Energy Landscape (FEL), and intrinsic molecular motions induced by the mutation, suggesting structural destabilization that could disrupt its function. This observed destabilization in RAD51C due to mutations offers valuable insights that may serve as diagnostic markers for individuals carrying these mutations, particularly in Fanconi anemia.
    Journal
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    RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
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    RAD51C mutation • RAD51 mutation
    4ms
    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)
    |
    FANCA deletion
    |
    Zejula (niraparib)
    5ms
    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
    |
    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
    5ms
    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)
    5ms
    Oncologic outcomes of incidental serous tubal intraepithelial carcinoma and associated high-grade serous carcinoma in high-risk patients undergoing risk-reducing surgery. (PubMed, Int J Gynecol Cancer)
    The study supports the critical need for timely risk-reducing surgery in high-risk populations, as well as a comprehensive pathologic examination along with vigilant post-operative surveillance. Consensus guidelines for management of serous tubal intraepithelial carcinoma are necessary to identify a group of patients at higher risk of progression to primary peritoneal carcinoma and optimize patient care.
    Journal • Surgery
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
    5ms
    Germline genetic variants in a case of familial cancer: RAD51D and four other co-segregated variants. (PubMed, J Genet)
    All the four family members show segregation of RAD51D (rs200564819). Other incidental findings ADAMTS13 (rs142572218) and SYCE1 (rs201873178) genetic variants in proband and son, and LIAS (rs546751789) and PDHA1(rs747051654) genetic variants in son have also been reported.
    Journal
    |
    RAD51D (RAD51 paralog D) • LIAS (Lipoic Acid Synthetase) • PDHA1 (Pyruvate Dehydrogenase E1 Subunit Alpha 1)
    6ms
    Germline variants of homology-directed repair or mismatch repair genes in cervical cancer. (PubMed, Int J Cancer)
    Taken together, our study supports a potentially risk-modifying role of MMR and HDR germline variants in cervical cancer but no association with HPV-negative status. These variants may be exploitable in future therapeutic managements.
    Journal • Mismatch repair • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSH6 (MutS homolog 6) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • FANCM (FA Complementation Group M) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)
    6ms
    RAD51 Paralogs and RAD51 Paralog Complexes BCDX2 and CX3 Interact with BRCA2. (PubMed, bioRxiv)
    Furthermore, the interaction with RAD51B is dependent upon an FxxA motif located on a surface exposed region of the CTD. Our study has identified novel interactions between the RAD51 paralogs and BRCA2 and further demonstrated that a previously unrecognized FxxA motif located within a mobile element of RAD51B is critical for the interaction.
    Journal • BRCA Biomarker • PARP Biomarker
    |
    BRCA2 (Breast cancer 2, early onset) • RAD51 (RAD51 Homolog A) • RAD51B (RAD51 Paralog B) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • XRCC2 (X-Ray Repair Cross Complementing 2) • XRCC3 (X-Ray Repair Cross Complementing 3)
    |
    RAD51C mutation • RAD51D mutation • RAD51B mutation • RAD51 mutation
    6ms
    TRIUMPH: Trial of Rucaparib in Patients With Metastatic Hormone-Sensitive Prostate Cancer Harboring Germline DNA Repair Gene Mutations (clinicaltrials.gov)
    P2, N=12, Completed, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Active, not recruiting --> Completed | N=30 --> 12
    Trial completion • Enrollment change • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCL (FA Complementation Group L) • FANCI (FA Complementation Group I) • FANCM (FA Complementation Group M) • 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)
    |
    CHEK2 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD50 mutation • FANCF mutation • NBN mutation • FANCG mutation • FANCI mutation • FANCM mutation
    |
    Rubraca (rucaparib)
    6ms
    TBCRC 048: Olaparib in Metastatic Breast Cancer (clinicaltrials.gov)
    P2, N=114, Active, not recruiting, Beth Israel Deaconess Medical Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Jul 2024 --> Jul 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset) • 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) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)
    |
    BRCA2 mutation • BRCA1 mutation • HR positive • PALB2 mutation • PGR positive • BRCA mutation
    |
    Lynparza (olaparib)
    6ms
    Prevalence and outcomes of germline pathogenic variants of homologous recombination repair genes in ovarian cancer. (PubMed, Cancer Sci)
    Variants were significantly associated with serous carcinoma and advanced disease, underscoring the importance of genetic testing to develop individualized EOC treatment strategies. Considering the study period (2000-2019), the limited use of bevacizumab and poly (ADP-ribose) polymerase inhibitors as maintenance therapy should be recognized.
    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) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
    |
    Avastin (bevacizumab)