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    BIOMARKER:

    DRD

    i
    Other names: DRD, DNA Repair Deficiency
    over1year
    Salubrious effects of proanthocyanidins on behavioral phenotypes and DNA repair deficiency in the BTBR mouse model of autism. (PubMed, Saudi Pharm J)
    In addition, proanthocyanidins reduced the elevated oxidative stress and recovered the disrupted DNA repair mechanism in the autistic animals by decreasing the expressions of Gadd45a and Parp1 levels and enhancing the expressions of Ogg1, P53, and Xrcc1 genes. This indicates that proanthocyanidins have significant potential as a new therapeutic strategy for alleviating autistic features.
    Preclinical • Journal • PARP Biomarker
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    TP53 (Tumor protein P53) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • OGG1 (8-Oxoguanine DNA glycosylase) • DRD (DNA Repair Deficiency) • XRCC1 (X-Ray Repair Cross Complementing 1)
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    DDR • TP53 expression • DRD
    over1year
    Impact of DNA Repair Deficiency in the Evolving Treatment Landscape of Bladder Cancer. (PubMed, Curr Urol Rep)
    There are now ongoing efforts to combine DDR inhibitors with the newest bladder cancer therapies, such as antibody-drug conjugates. This review highlights the most recent advances in targeting DNA repair deficiency in the evolving treatment landscape of bladder cancer.
    Review • Journal • PARP Biomarker • IO biomarker
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    DRD (DNA Repair Deficiency)
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    DDR • DRD
    over1year
    ASCLEPIuS: A Multi-Center Trial of Androgen Suppression With Abiraterone Acetate, Leuprolide, PARP Inhibition and Stereotactic Body Radiotherapy in Prostate Cancer (clinicaltrials.gov)
    P1/2, N=102, Active, not recruiting, University of Michigan Rogel Cancer Center | Recruiting --> Active, not recruiting
    Enrollment closed
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    DRD (DNA Repair Deficiency)
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    DDR • DRD
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    Zejula (niraparib) • abiraterone acetate • leuprolide acetate for depot suspension
    over1year
    Datopotamab-deruxtecan in early-stage breast cancer: the sequential multiple assignment randomized I-SPY2.2 phase 2 trial. (PubMed, Nat Med)
    I-SPY2.2 uses a sequential multiple assignment randomization trial design that includes three sequential blocks of biologically targeted neoadjuvant treatment: the experimental agent(s) (block A), a taxane-based regimen tailored to the tumor subtype (block B) and doxorubicin-cyclophosphamide (block C). Dato-DXd was particularly active in the hormone receptor-negative/HER2-Immune-DNA repair deficiency- signature, warranting further investigation, and was safe in other subtypes in patients who followed the treatment strategy. ClinicalTrials.gov registration: NCT01042379 .
    P2 data • Journal
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    HER-2 (Human epidermal growth factor receptor 2) • DRD (DNA Repair Deficiency)
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    HER-2 negative • DDR • HR negative • DRD • HER-2 negative + HR negative
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    doxorubicin hydrochloride • cyclophosphamide • Datroway (datopotamab deruxtecan-dlnk)
    over1year
    Triple-Negative Breast Cancer: Molecular Particularities Still a Challenge. (PubMed, Diagnostics (Basel))
    This ongoing research is essential for improving the management and outcomes of TNBC, which is a challenging and heterogeneous form of breast cancer. The findings of this research have practical implications for refining treatment strategies, particularly in selecting appropriate systemic therapies and integrating traditional treatment modalities like surgery and radiotherapy into comprehensive care plans for TNBC patients.
    Review • Journal
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    DRD (DNA Repair Deficiency)
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    DDR • DRD • HRD signature
    over1year
    Tumour immune characterisation of primary triple-negative breast cancer using automated image quantification of immunohistochemistry-stained immune cells. (PubMed, Sci Rep)
    The digital cell counts demonstrated how immune markers are coexpressed in the TIME when considering TNBC molecular subtypes and DNA repair deficiency, and how combination of immune status with DNA repair deficiency status can improve the prognostic stratification in chemotherapy treated patients. These results underscore the value and potential of integrating TIME and specific tumour intrinsic alterations/phenotypes for the molecular understanding of TNBC.
    Journal • PD(L)-1 Biomarker • IO biomarker • Immune cell
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    CD20 (Membrane Spanning 4-Domains A1) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • CD68 (CD68 Molecule) • FOXP3 (Forkhead Box P3) • DRD (DNA Repair Deficiency)
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    DDR • DRD
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    VENTANA PD-L1 (SP142) Assay
    almost2years
    Expression of DNA Repair Genes in Ewing Sarcoma. (PubMed, Cancer Diagn Progn)
    In addition, low expression of the xrcc4 gene has been associated with better overall survival probability (p=0.032). Our results, even though retrospective and in a small number of patients, highlight the importance of DSBs repair and propose a potential therapeutic target for this type of sarcoma.
    Review • Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51 (RAD51 Homolog A) • EWSR1 (EWS RNA Binding Protein 1) • FLI1 (Fli-1 Proto-Oncogene ETS Transcription Factor) • RAD52 (RAD52 Homolog DNA Repair Protein) • DRD (DNA Repair Deficiency) • NT5C (5', 3'-Nucleotidase, Cytosolic) • FANCC (FA Complementation Group C)
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    DDR • DRD
    almost2years
    Antileukemic potential of methylated indolequinone MAC681 through immunogenic necroptosis and PARP1 degradation. (PubMed, Biomark Res)
    Overall, increasing the tumor mutational burden by PARP1 degradation and mitochondrial deregulation makes CML suitable for immunotherapy.
    Journal • Tumor mutational burden • BRCA Biomarker • PARP Biomarker • IO biomarker
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    TMB (Tumor Mutational Burden) • BRCA (Breast cancer early onset) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • CALR (Calreticulin) • DRD (DNA Repair Deficiency)
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    DDR • BRCA mutation • DRD
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    imatinib • Scemblix (asciminib)
    almost2years
    NIRADO: Basket Trial Exploring the Efficacy and Safety of the Combination of Niraparib and Dostarlimab (clinicaltrials.gov)
    P2, N=51, Suspended, Gustave Roussy, Cancer Campus, Grand Paris | N=112 --> 51 | Trial completion date: Mar 2027 --> Dec 2027 | Recruiting --> Suspended | Trial primary completion date: Mar 2024 --> Dec 2024
    Enrollment change • Trial completion date • Trial suspension • Trial primary completion date • Pan tumor
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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 • PBRM1 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • BARD1 mutation • NBN mutation • DRD
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    Zejula (niraparib) • Jemperli (dostarlimab-gxly)
    almost2years
    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, Suspended, Gustave Roussy, Cancer Campus, Grand Paris | N=1000 --> 130 | Trial primary completion date: Apr 2024 --> Dec 2024
    Enrollment change • Trial primary completion date • Pan tumor
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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 • FANCA mutation • RAD51D mutation • BARD1 mutation • NBN mutation • DRD
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    Tecentriq (atezolizumab) • Rubraca (rucaparib)
    almost2years
    Biallelic EPCAM deletions induce tissue-specific DNA repair deficiency and cancer predisposition. (PubMed, NPJ Precis Oncol)
    In contrast, maturation into brain organoids and examination of blood and fibroblasts failed to show similar processes, preserving MMR proficiency. The combined use of iPSC, organoid technologies and functional genomics analyses highlights the potential of cutting-edge cellular and molecular analysis techniques to define processes controlling tumorigenesis and uncovers a new paradigm of tissue-specific MMRD, which affects the clinical management of these patients.
    Journal • Tumor mutational burden
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    TMB (Tumor Mutational Burden) • MSH2 (MutS Homolog 2) • EPCAM (Epithelial cell adhesion molecule) • DRD (DNA Repair Deficiency)
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    DDR • DRD • EPCAM expression
    2years
    Deposition of onco-histone H3.3-G34W leads to DNA repair deficiency and activates cGAS/STING-mediated immune responses. (PubMed, Int J Cancer)
    Together with defective cell cycle checkpoints reported previously, this DNA repair deficiency in H3.3-G34W cells led to accumulation of micronuclei and cytosolic DNA following IR, which subsequently led to activation of the cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING) pathway, thereby inducing release of immune-stimulatory cytokines. These findings suggest a potential for radiotherapy for tumors expressing H3.3-G34W, which can be further improved by combination with STING agonists to induce immune-mediated therapeutic efficacy.
    Journal
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    STING (stimulator of interferon response cGAMP interactor 1) • CGAS (Cyclic GMP-AMP Synthase) • DRD (DNA Repair Deficiency)
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    DDR • DRD