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    GENE:

    BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1)

    i
    Other names: BRCA1 Interacting Protein C-Terminal Helicase 1, BRCA1-Associated C-Terminal Helicase 1, BRCA1/BRCA2-Associated Helicase 1, ATP-Dependent RNA Helicase BRIP1, Fanconi Anemia Group J Protein, BACH1, FANCJ, BRCA1-Binding Helicase-Like Protein BACH1, BRCA1-Interacting Protein 1, Protein FACJ, BRCA1 Interacting Protein C-terminal Helicase 1
    4d
    Role and Mechanism of BRIP1 in Anoikis Resistance of Gastric Cancer. (PubMed, Int J Mol Sci)
    We found that the PI3K inhibitor LY294002 counteracted BRIP1-driven oncogenic effects, which was evidenced by restored expression of key regulators governing apoptosis, cell cycle progression, and EMT, in addition to suppressed proliferation in GC cells. BRIP1 is postulated to function upstream of the PI3K/Akt signaling cascade. This study establishes a risk scoring model and identifies BRIP1 as a potential prognostic marker for GC.
    Journal
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    BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • TXNIP (Thioredoxin Interacting Protein) • DUSP1 (Dual Specificity Phosphatase 1)
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    LY294002
    9d
    Integrating breast tumour homologous recombination deficiency status to aid germline BRCA1 and BRCA2 variant classification. (PubMed, EBioMedicine)
    Analysis across multiple tumour whole-genome sequencing datasets has shown that HR status prediction algorithms can separate profiles for BRCA1 and BRCA2 pathogenic variants and provide further evidence at increased weight to aid in the classification of germline BRCA1 and BRCA2 variants. Tumour sequencing offers a promising strategy for reducing the uncertainty in germline variant interpretation.
    Journal • BRCA Biomarker
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    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset) • 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)
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    HRD
    13d
    Identification of Genetic Variants Among Breast Cancer Patients and At-Risk Individuals: A Cohort Study in Sri Lanka. (PubMed, Breast Cancer (Auckl))
    Three pathogenic variants, BRCA2 [c.6509A>G; c.7879A>T; c.5574_5577delAATT] and PALB2 [c.1592delT], were identified in high-risk genes important for breast cancer prediction. Identification of population-based variants may improve breast cancer screening and management in Sri Lanka.
    Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • NF1 (Neurofibromin 1) • PALB2 (Partner and localizer of BRCA2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • MUTYH (MutY homolog)
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    BRCA2 mutation • PALB2 mutation
    20d
    BRIP1-Mediated RINT1 Acetylation and NF-κB Activation Promote DNA Repair and Immunosuppressive Microenvironment in Lung Adenocarcinoma. (PubMed, Cancer Lett)
    In vivo, BRIP1 overexpression accelerates tumor growth and metastasis while conferring resistance to PD-L1 blockade, which is effectively reversed by combining anti-PD-L1 therapy with STING activation. Collectively, our findings establish BRIP1 as a molecular link between DNA repair proficiency and immune suppression in LUAD, highlighting BRIP1-associated pathways as actionable targets for rational combination immunotherapy.
    Journal • PD(L)-1 Biomarker • IO biomarker
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    BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD50 (RAD50 Double Strand Break Repair Protein) • STING (stimulator of interferon response cGAMP interactor 1) • ALKBH5 (AlkB Homolog 5, RNA Demethylase)
    27d
    SPORE: A Study of Pembrolizumab and Olaparib for People With Metastatic Pancreatic Ductal Adenocarcinoma and Homologous Recombination Deficiency or Exceptional Treatment Response to Platinum-Based Therapy (clinicaltrials.gov)
    P2, N=63, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jan 2026 --> Jan 2027 | Trial primary completion date: Jan 2026 --> Jan 2027
    Trial completion date • Trial primary completion date
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • BAP1 (BRCA1 Associated Protein 1) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • ABRAXAS1 (Abraxas 1 BRCA1 A Complex Subunit 2) • FANCC (FA Complementation Group C)
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    MSK-IMPACT
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    Keytruda (pembrolizumab) • Lynparza (olaparib)
    28d
    PARPi-PANC: Niraparib as First Line Therapy With Metastatic Homologous Repair-deficient Pancreatic Cancer (clinicaltrials.gov)
    P2, N=2, Terminated, Centre Leon Berard | Withdrawn --> Terminated; Study not feasible, patient accrual rate too low.
    Trial termination
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • 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) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha) • FANCD2 (FA Complementation Group D2)
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    Zejula (niraparib)
    1m
    Discovering Hereditary Risk Through Surveillance: A Prospective Genetic Analysis of Individuals With Familial Pancreatic Cancer. (PubMed, United European Gastroenterol J)
    Integrating germline testing into surveillance redefines the management of familial PC. It uncovers hereditary susceptibility beyond classical criteria and supports cascade testing. PC also arises in mutation-negative HRI. #NCT05724992.
    Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • MUTYH (MutY homolog) • SPINK1 (Serine peptidase inhibitor, kazal type 1) • CTRC (Chymotrypsin C)
    1m
    The Contribution of Genetic Modifiers to Ovarian Cancer Risk in BRCA1 and BRCA2 Pathogenic Variant Carriers. (PubMed, Cancers (Basel))
    The analysis identified 11 variants affecting both BRCA1 and BRCA2 carriers, most of which increase risk, including the following: IRS1, RSPO1, SYNPO2, BABAM1, MRPL34, PLEKHM1, and TIPARP...The only SNP reaching genome-wide significance (p < 5 × 10-8) was in BNC2. The article summarizes the growing number of genetic modifiers of ovarian cancer risk among BRCA1/2 carriers and highlights their potential to improve individualized risk assessment, enhance patient stratification, support personalized prevention and surveillance strategies, deepen the understanding of disease biology, and identify potential therapeutic targets.
    Review • Journal
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRAS (Harvey rat sarcoma viral oncogene homolog) • BRCA (Breast cancer early onset) • RAD51 (RAD51 Homolog A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • MTHFR (Methylenetetrahydrofolate Reductase) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • CASP8 (Caspase 8) • PARP2 (Poly(ADP-Ribose) Polymerase 2) • RSPO1 (R-Spondin 1) • TIPARP (TCDD Inducible Poly(ADP-Ribose) Polymerase) • ITGB3 (Integrin Subunit Beta 3)
    1m
    Pembrolizumab, Olaparib, and Temozolomide for People With Glioma (clinicaltrials.gov)
    P2, N=57, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jan 2026 --> Jan 2027 | Trial primary completion date: Jan 2026 --> Jan 2027
    Trial completion date • Trial primary completion date
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    EGFR (Epidermal growth factor receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • FGFR (Fibroblast Growth Factor Receptor) • CDK12 (Cyclin dependent kinase 12) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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    CDKN2A deletion • BRIP1 mutation • RAD51C mutation • RAD51B mutation • BARD1 mutation • IDH wild-type
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    Keytruda (pembrolizumab) • Lynparza (olaparib) • temozolomide
    1m
    The neuronal ALAS2/5-ala axis mitigates chemotherapy-induced neurotoxicity via the BACH1/NRF2 pathway. (PubMed, Br J Pharmacol)
    In conclusion, this study elucidates a novel endogenous neuroprotective mechanism wherein the ALAS2/5-ALA axis modulates the BACH1/NRF2 pathway. 5-ALA shows promise for repurposing to mitigate chemotherapy-associated neurotoxicity.
    Journal • IO biomarker
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    BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • BACH1 (BTB Domain And CNC Homolog 1)
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    doxorubicin hydrochloride
    1m
    Phase II Trial of the PARP Inhibitor Niraparib and PD-1 Inhibitor Dostarlimab in Patients With Advanced Cancers With Active Progressing Brain Metastases (STARLET) (clinicaltrials.gov)
    P2, N=120, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Feb 2026 --> Dec 2029 | Trial primary completion date: Feb 2026 --> Dec 2029
    Trial completion date • Trial primary completion date
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    PD-L1 (Programmed death ligand 1) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog 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) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • RAD52 (RAD52 Homolog DNA Repair Protein)
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    PD-L1 expression
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    Zejula (niraparib) • Jemperli (dostarlimab-gxly)
    2ms
    Clinical and Prognostic Relevance of BRIP1 Expression in Colorectal Cancer: Evidence from TCGA and Korean Cohorts. (PubMed, Medicina (Kaunas))
    Lower BRIP1 mRNA expression is significantly associated with aggressive clinicopathological features and poor prognosis in CRC. BRIP1 may serve as a promising biomarker for risk stratification and a potential therapeutic target in the management of CRC.
    Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • MSI (Microsatellite instability) • CEACAM5 (CEA Cell Adhesion Molecule 5) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1)
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    BRIP1 mutation