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    GENE:

    HRD (Homologous Recombination Deficiency)

    i
    Other names: HRD, Homologous Recombination Deficiency, HRR, Homologous recombination repair
    1d
    Alkylating agents activate an SLFN11-dependent vulnerability that confers PARP-1 inhibitor sensitivity in kidney cancer. (PubMed, J Exp Clin Cancer Res)
    Our findings reveal an intrinsic SLFN11-dependent vulnerability in ccRCC that synergizes with alkylating agents to induce an acquired PARP-1 dependency, thereby sensitizing BRCA1/2-WT tumors to PARP inhibition. Therefore, this work uncovers a potential therapeutic strategy for targeting SLFN11-high kidney cancers.
    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) • SLFN11 (Schlafen Family Member 11)
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    BRCA2 mutation • BRCA1 mutation • BRCA wild-type
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    Lynparza (olaparib) • temozolomide • Zanosar (streptozocin)
    2d
    Immune Evasion in Ovarian Cancer Peritoneal Metastasis: Mechanisms and Biomarker-Guided Therapeutic Matching. (PubMed, J Cell Physiol)
    Finally, we propose a biomarker-guided framework that links antigen-presentation competence, immune engagement, dominant suppressive axes, and ascites-specific biology to rational therapeutic matching. This mechanism-centered view supports more precise trial design and provides a roadmap for combination immunotherapy in advanced ovarian cancer.
    Review • Journal • PARP Biomarker • IO biomarker
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    HRD (Homologous Recombination Deficiency)
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    HRD
    3d
    A decision-oriented framework for genomic testing across the prostate cancer continuum. (PubMed, Cancer Genet)
    We further address implementation barriers that may limit real-world impact, including reimbursement uncertainty, disparities in access to next-generation sequencing, limited provider familiarity with genomic interpretation, and the need for patient-centered communication and navigation in genomics-informed care. A clinically useful framework for prostate cancer genomics must therefore move beyond cataloging tests and instead clarify when genomic results change management, where evidence remains immature, and how implementation strategies can improve equity and actionability.
    Journal
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    HRD (Homologous Recombination Deficiency)
    3d
    Gineco-ov133b: REGENOVAR: A Phase I/II Study of Ubamatamab Plus Carboplatin, Paclitaxel, and Bevacizumab as Salvage Therapy in Ovarian Cancer with Poor Response to First-Line Chemotherapy. (2025-524232-20-00)
    P1/2, N=43, Not yet recruiting, Asso De Recherche Cancers Gynecologiques
    New P1/2 trial
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    HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)
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    HRD
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    Avastin (bevacizumab) • carboplatin • paclitaxel • ubamatamab (REGN4018) • Neupogen (filgrastim)
    4d
    RAD21 regulation of the enhancer-promoter chromatin loop of RAD51 promotes PARPi resistance in ovarian cancer. (PubMed, J Transl Med)
    Our findings in this study indicate that RAD21 could serve as a potential therapeutic target for overcoming olaparib resistance in ovarian cancer, and provide new insights into the mechanisms underlying the resistance to PARPi from the perspective of chromatin organization.
    Journal • PARP Biomarker
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    HRD (Homologous Recombination Deficiency) • RAD51 (RAD51 Homolog A) • RAD21 (RAD21 Cohesin Complex Component)
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    Lynparza (olaparib)
    5d
    Beyond PARP-HDAC inhibition: mechanistic rationale and medicinal chemistry insights from single to shared-target strategies. (PubMed, Bioorg Chem)
    Furthermore, the review discusses several shared and interconnected therapeutic targets that have been explored in combination or hybrid strategies with PARP or HDAC inhibition, including tubulin, proteasome, EGFR, VEGFR2, CDKs, topoisomerase I and II, EZH2, BRD4, and c-MET. Understanding these interconnected pathways may facilitate the development of next-generation multitarget anticancer agents with improved efficacy and reduced resistance.
    Review • Journal
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    EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase) • HRD (Homologous Recombination Deficiency) • KDR (Kinase insert domain receptor) • BRD4 (Bromodomain Containing 4)
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    HRD
    5d
    MK3475-A53: Study of SBRT/Olaparib Followed by Pembrolizumab/Olaparib in Gastric Cancers (clinicaltrials.gov)
    P2, N=9, Completed, University of Colorado, Denver | Active, not recruiting --> Completed | Trial completion date: Dec 2028 --> Jan 2026
    Trial completion • Trial completion date
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    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) • HRD (Homologous Recombination Deficiency) • BAP1 (BRCA1 Associated Protein 1) • KMT2D (Lysine Methyltransferase 2D) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD50 (RAD50 Double Strand Break Repair Protein) • MLL2 (Myeloid/lymphoid or mixed-lineage leukemia 2) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • WRN (WRN RecQ Like Helicase) • FANCG (FA Complementation Group G) • ABRAXAS1 (Abraxas 1 BRCA1 A Complex Subunit 2) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)
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    HRD
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    Keytruda (pembrolizumab) • Lynparza (olaparib)
    6d
    A pan-cancer landscape of LILRB4 identifies it as a context-dependent marker of the myeloid and antigen-presentation axis. (PubMed, Transl Oncol)
    LILRB4 correlates strongly with macrophage infiltration, and co-expression and interaction analyses converge on antigen processing and presentation pathways, with HLA-DRA emerging as a shared node. Collectively, these findings support LILRB4 as a context-dependent marker of the myeloid and antigen-presentation axis in the tumor microenvironment and provide an integrated reference framework that warrants further functional validation.
    Journal • Tumor mutational burden • Pan tumor
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    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • HRD (Homologous Recombination Deficiency) • HLA-DRA (Major Histocompatibility Complex, Class II, DR Alpha) • LILRB4 (Leukocyte Immunoglobulin Like Receptor B4)
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    HRD
    6d
    Clinical relevance of homologous recombination repair gene alterations in endometrial cancer patients in the era of molecular classification. (PubMed, Gynecol Oncol)
    HRD was rare and associated with aggressive biological features, but it did not have a prognostic value. These findings suggest that integrated molecular classification is paramount for risk stratification in EC, and that HRD, as currently defined, should not be used as an isolated biomarker for clinical decision-making.
    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)
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    HRD
    7d
    Tuvusertib Combined With Niraparib or Lartesertib in Participants With Epithelial Ovarian Cancer (DDRiver EOC 302) (clinicaltrials.gov)
    P2, N=63, Active, not recruiting, EMD Serono Research & Development Institute, Inc. | Trial primary completion date: Sep 2025 --> Jun 2026
    Trial primary completion date
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency)
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    BRCA1 mutation • HRD
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    Zejula (niraparib) • tuvusertib (M1774) • lartesertib (M4076)
    7d
    Deep learning-based prediction of homologous recombination deficiency from histopathological whole-slide images in ovarian cancer. (PubMed, Int J Gynecol Cancer)
    Our results demonstrate that deep learning applied to whole-slide images can predict homologous recombination deficiency status with clinically meaningful accuracy and strong generalization across datasets. The model is particularly effective at identifying homologous recombination-proficient patients and may serve as a valuable tool to support or triage molecular testing. Integrating this artificial intelligence tool into routine pathology workflows could improve diagnostic efficiency, reduce costs, and accelerate access to targeted therapies in ovarian cancer.
    Journal • BRCA Biomarker
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    HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)
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    HRD • BRCA wild-type
    7d
    MND1 reduces breast cancer chemosensitivity by promoting RAD51-mediated homologous recombination repair. (PubMed, Cell Death Dis)
    We demonstrated that MND1 is upregulated in breast cancer and associated with cancer progression and cisplatin resistance...Our findings establish a role for MND1 in regulating chemosensitivity and provide new insights into relevant gene interaction networks. The identified E2F1/MND1/USP5/RAD51 feedback loop underscores the potential of MND1 as a therapeutic target for breast cancer.
    Journal
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    HRD (Homologous Recombination Deficiency) • RAD51 (RAD51 Homolog A) • E2F1 (E2F transcription factor 1) • MND1 (Meiotic Nuclear Divisions 1) • USP5 (Ubiquitin Specific Peptidase 5)
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    cisplatin