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    GENE:

    BRCA2 (Breast cancer 2, early onset)

    i
    Other names: BRCA2, BRCC2, FACD, FAD, FAD1, FANCD, FANCD1, Breast cancer 2, early onset
    1d
    STAR-BREAST: Screening Tool Artificial Intelligence-based for Predicting the Genetic Risk of BREAST Cancer (clinicaltrials.gov)
    P=N/A, N=800, Recruiting, AstraZeneca | Not yet recruiting --> Recruiting
    Enrollment open
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    BRCA2 (Breast cancer 2, early onset)
    1d
    A phase Ib study of sapacitabine and olaparib in patients with BRCA1/2-mutated metastatic breast cancer. (PubMed, Clin Cancer Res)
    Sapacitabine with olaparib produces high rates of hematologic toxicity. However, the ORR of 50%, mPFS of 9.7 months, and durability of response in some patients suggest possible combinatorial benefit. Further exploration of olaparib with different sapacitabine schedules or substitution of a PARP1-selective inhibitor to potentially decrease hematological toxicity is warranted.
    P1 data • Journal • BRCA Biomarker • PARP Biomarker
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    HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)
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    HER-2 negative • BRCA mutation
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    Lynparza (olaparib) • sapacitabine (CYC682)
    2d
    Sentinel Lymph Node Biopsy for Prophylactic Mastectomy: Necessary Precaution or Unnecessary Procedure? (PubMed, Ann Surg Oncol)
    Occult malignancy was uncommon, and SLNB positivity was exceedingly rare in prophylactic NSMs. Routine SLNB is not justified in this setting and should be reserved for select higher-risk scenarios. Personalized, risk-adapted approaches to axillary management and preoperative imaging are warranted.
    Journal
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset)
    3d
    NIRADO: Basket Trial Exploring the Efficacy and Safety of the Combination of Niraparib and Dostarlimab (clinicaltrials.gov)
    P2, N=51, Terminated, Gustave Roussy, Cancer Campus, Grand Paris | Trial completion date: Dec 2027 --> Feb 2025 | Suspended --> Terminated; Abandon of the partner, GSK
    Trial completion date • Trial termination • Pan tumor • Platinum sensitive
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    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) • ARID1A (AT-rich interaction domain 1A) • PBRM1 (Polybromo 1) • CDK12 (Cyclin dependent kinase 12) • 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) • RAD51D (RAD51 paralog D) • ARID2 (AT-Rich Interaction Domain 2) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • DRD (DNA Repair Deficiency)
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    HER-2 positive • HER-2 amplification • DDR • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • BARD1 mutation
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    Zejula (niraparib) • Jemperli (dostarlimab-gxly)
    3d
    Computationally-designed aptamers targeting RAD51-BRCA2 interaction impair homologous recombination and induce synthetic lethality. (PubMed, Nat Commun)
    Notably, when combined with the PARP inhibitor olaparib, the aptamer triggers synthetic lethality (SL) in a dose-dependent manner, an effect that is also preserved in 3D spheroid models. Our study showcases an aptamer-based approach for selectively targeting protein interactions within DNA repair pathways, introducing a promising avenue for SL-based treatments applicable to a wide range of cancers.
    Journal
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    BRCA2 (Breast cancer 2, early onset) • RAD51 (RAD51 Homolog A)
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    Lynparza (olaparib)
    3d
    ARIANES: Efficacy and Safety of the Combination of Rucaparib (PARP Inhibitor) and Atezolizumab (Anti-PD-L1 Antibody) in Patients With DNA Repair-deficient or Platinum-sensitive Solid Tumors (clinicaltrials.gov)
    P2, N=130, Terminated, Gustave Roussy, Cancer Campus, Grand Paris | Suspended --> Terminated; Bankruptcy of partner: Clovis
    Trial termination • Pan tumor • Platinum sensitive
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    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) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • IL2 (Interleukin 2) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • DRD (DNA Repair Deficiency)
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    DDR • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • BARD1 mutation
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    Tecentriq (atezolizumab) • Rubraca (rucaparib)
    3d
    Comprehensive genomic profiling for homologous recombination deficiency guides PARP inhibitor therapy recommendations in ovarian cancer. (PubMed, Pathol Oncol Res)
    PARPi selection differed by HRD status, with niraparib favored in HR-proficient and olaparib in HRD-positive tumors. No additional profiling was required for PARPi therapy recommendation, and no incidental findings beyond the scope of HRD testing were detected. Molecular profiling with F1CDx proved to be a technically feasible, clinically impactful, and time-efficient assay, demonstrating its value in supporting molecular-guided PARPi therapy recommendations in the routine care of HGSOC patients.
    Retrospective data • Journal • BRCA Biomarker • PARP Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)
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    HRD • BRCA mutation
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    FoundationOne® CDx
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    Lynparza (olaparib) • Zejula (niraparib)
    4d
    Overcoming Radioresistance in Prostate Cancer by Targeting DNA Damage Repair. (PubMed, Cancer Lett)
    We further explore the interplay of DDR inhibition with androgen receptor (AR) signaling and its ability to potentiate antitumor immunity through activation of the cGAS-STING pathway, type I interferon production, and regulation of immune checkpoints. By leveraging insights into DDR mechanisms and therapeutic opportunities, this review provides a comprehensive perspective to enhance RT efficacy and improve clinical outcomes in PCa patients.
    Review • Journal • BRCA Biomarker • PARP Biomarker
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    BRCA2 (Breast cancer 2, early onset) • PARP1 (Poly(ADP-Ribose) Polymerase 1)
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    ATM mutation
    5d
    Functional analysis of BRCA1 and BRCA2 splicing variants using a minigene assay. (PubMed, Hum Genomics)
    Finally aberrant splicing patterns were found in three of the four variants: BRCA1:c.80 + 3_80 + 5del, BRCA1:c.548-15G > A, BRCA2:c.8755-19 A > G that were previously classified as VUS through experimental analysis. As a result, we reclassify BRCA1;c.80 + 3_80 + 5del as LP and we classify BRCA1;c.548-15G > A and BRCA2;c.8755-19 A > G as VUS.
    Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)
    5d
    Changes in life decisions and in emotions following genetic testing for cancer risk. (PubMed, BMC Psychol)
    In the second area, two main themes related to personal and social changes, which were further divided into five sub-themes, were identified. Future studies could explore how to better address emotional and behavioral challenges faced by BRCA1/2 carriers, by providing adequate psychological support and improving doctor-patient communication.
    Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)
    6d
    Towards antibody-based immunotherapy development for platinum-resistant high-grade serous ovarian cancer. (PubMed, Sci Rep)
    Significant killing efficiencies were achieved using antibodies against breast cancer cells (S2) and antibody against CD59 (Yht53.1) regardless whether the cell lines HGSOC (OVCAR-3, OVCAR-8) or CRISPR-Cas9 BRCA2 deleted OVCAR-4 were homologous recombination (HR) deficient or proficient, Pt sensitive or resistant. This work shows a potential towards antibody-based therapy development for Pt-resistant HGSOC.
    Journal • Platinum resistant
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    BRCA2 (Breast cancer 2, early onset) • ANXA5 (Annexin A5) • CD59 (CD59 Molecule)