^
    1d
    NCI protocol 10250: A Phase II Clinical Trial Evaluating the Combination of Olaparib and Temozolomide for the Treatment of Advanced Uterine Leiomyosarcoma (clinicaltrials.gov)
    P2, N=23, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2026 --> Nov 2026
    Trial completion date
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    SLFN11 (Schlafen Family Member 11)
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    Lynparza (olaparib) • temozolomide
    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
    Development of a liquid overlay-based three-dimensional cell culture panel for drug screening applications. (PubMed, Sci Rep)
    Afterwards, the cytostatic and cytotoxic responses of these models to three targeted anti-PARP therapies, Olaparib, Rucaparib and Niraparib, were analyzed, revealing their sensitivity. These results demonstrated that our liquid overlay-based technique provides both a large cell culture panel, whatever the tissue type or pathological level, and an automated drug screening process that could lead to highly predictive efficacy results.
    Preclinical • Journal
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    PARP1 (Poly(ADP-Ribose) Polymerase 1)
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    Lynparza (olaparib) • Zejula (niraparib) • Rubraca (rucaparib)
    2d
    ONITT: Study of Onivyde With Talazoparib or Temozolomide in Children With Recurrent Solid Tumors and Ewing Sarcoma (clinicaltrials.gov)
    P1/2, N=90, Recruiting, St. Jude Children's Research Hospital | Active, not recruiting --> Recruiting | N=46 --> 90
    Enrollment open • Enrollment change
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    EWSR1 (EWS RNA Binding Protein 1) • FLI1 (Fli-1 Proto-Oncogene ETS Transcription Factor)
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    temozolomide • Talzenna (talazoparib) • Onivyde (nanoliposomal irinotecan)
    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
    NeoSarc: Study Evaluating Pembrolizumab +/- Olaparib in TLS Positive Selected Resectable STS Followed by Adjuvant Pembrolizumab (clinicaltrials.gov)
    P2, N=0, Withdrawn, Gustave Roussy, Cancer Campus, Grand Paris | N=36 --> 0 | Recruiting --> Withdrawn
    Enrollment change • Trial withdrawal
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    Keytruda (pembrolizumab) • Lynparza (olaparib)
    4d
    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)
    4d
    EXO1 overexpression induces homologous recombination deficiency and enhances PARP inhibitor sensitivity in ER-positive breast cancer: modulation by N4BP2L2-Mediated restoration. (PubMed, Front Cell Dev Biol)
    Functional assays in both T47D and MCF7 cells demonstrated that co-expression of N4BP2L2 restored HR activity and reduced olaparib sensitivity in EXO1-overexpressing cells. These findings suggest EXO1 overexpression serves as a marker of functional HR deficiency and a potential predictor of PARP inhibitor response, highlighting the EXO1-N4BP2L2 axis as a promising biomarker and therapeutic target, especially for guiding PARP inhibitor use beyond BRCA-mutated tumors.
    Journal • BRCA Biomarker • PARP Biomarker
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    ER (Estrogen receptor) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset) • EXO1 (Exonuclease 1) • N4BP2L2 (NEDD4 Binding Protein 2 Like 2)
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    ER positive • HRD • BRCA mutation
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    Lynparza (olaparib)
    4d
    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)
    6d
    ANALLISA: Niraparib Rechallenge After Surgery in Ovarian Cancer Patients With Oligometastatic Progression (clinicaltrials.gov)
    P2, N=30, Recruiting, MedSIR | Trial completion date: Nov 2025 --> Jan 2028 | Trial primary completion date: Oct 2025 --> Jan 2028
    Trial completion date • Trial primary completion date
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    Zejula (niraparib)
    6d
    SLC7A5-ERBB2 axis drives olaparib resistance via de novo lipid synthesis in ovarian cancer. (PubMed, Oncogene)
    Mechanistically, SLC7A5 upregulates ERBB2 transcription through ELK1, and ERBB2 competes with CUL3 to prevent ACLY degradation. These findings suggest that targeting SLC7A5 may reverse olaparib resistance, offering new strategies for combination therapies and improving clinical outcomes in ovarian cancer treatment.
    Journal • PARP Biomarker
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    HER-2 (Human epidermal growth factor receptor 2) • SLC7A5 (Solute Carrier Family 7 Member 5)
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    Lynparza (olaparib)