^
    1d
    DUO-O: Durvalumab Treatment in Combination With Chemotherapy and Bevacizumab, Followed by Maintenance Durvalumab, Bevacizumab and Olaparib Treatment in Advanced Ovarian Cancer Patients (clinicaltrials.gov)
    P3, N=1407, Active, not recruiting, AstraZeneca | Trial completion date: Mar 2028 --> Dec 2026
    Trial completion date
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)
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    BRCA2 mutation • BRCA1 mutation
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    Avastin (bevacizumab) • Lynparza (olaparib) • carboplatin • Imfinzi (durvalumab) • paclitaxel
    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
    Case Report: Complete response to the novel NaPi2b-targeting ADC YL205 in heavily pretreated platinum-resistant ovarian cancer. (PubMed, Front Oncol)
    A 40-year-old woman with FIGO stage IVB, BRCA-wildtype HGSOC developed rapid multi-drug resistance following neoadjuvant chemotherapy, optimal cytoreduction, and progression on maintenance olaparib/bevacizumab, gemcitabine, and a USP1 inhibitor. By utilizing topoisomerase I inhibitors, agents like YL205 bypass microtubule-stabilization resistance induced by prior taxane exposure, while "bystander effects" address intratumoral heterogeneity. Longitudinal, biomarker-matched strategies and proactive toxicity management are essential to achieving deep tissue clearance in heavily pretreated HGSOC.
    Journal • BRCA Biomarker • PARP Biomarker • Platinum resistant
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    BRCA (Breast cancer early onset) • MUC16 (Mucin 16, Cell Surface Associated) • SLC34A2 (Solute carrier family 34 member 2) • USP1 (Ubiquitin Specific Peptidase 1)
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    BRCA wild-type
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    Avastin (bevacizumab) • Lynparza (olaparib) • gemcitabine
    2d
    DNER drives glycolytic reprogramming in renal cell carcinoma by activating the JAK2/STAT3 signaling pathway. (PubMed, Front Immunol)
    Preliminary evidence also suggests that DNER overexpression may be associated with enhanced sensitivity of ccRCC cells to the PARP inhibitor Olaparib, although the underlying mechanism requires further investigation. In conclusion, DNER drives ccRCC progression by coupling glycolytic reprogramming with immunosuppressive microenvironment formation via the JAK2/STAT3 signaling axis, and may represent a potential therapeutic target for ccRCC.
    Journal • PARP Biomarker
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    LDHA (Lactate dehydrogenase A)
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    Lynparza (olaparib)
    2d
    Multimodal therapy for ovarian cancer with brain metastases diagnosed synchronously at the initial phase: case report of a long-term survivor with comprehensive literature review. (PubMed, Gynecol Oncol Rep)
    Complete remission was obtained using stereotactic radiotherapy to the brain lesions, followed by platinum-based chemotherapy and maintenance therapy with bevacizumab and olaparib...Their role in this setting remains emerging and primarily supported by limited case reports and small series. Further studies are required to better define their role.
    Journal • BRCA Biomarker • PARP Biomarker
    |
    BRCA1 (Breast cancer 1, early onset)
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    BRCA1 mutation
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    Avastin (bevacizumab) • Lynparza (olaparib) • Zejula (niraparib)
    2d
    Expert Consensus on the Clinical Application of Poly ADP Ribose Polymerase Inhibitors in Breast Cancer (2025 Edition). (PubMed, Cancer Innov)
    Currently, PARP inhibitors such as Olaparib and Fluzoparib have been approved for clinical use. This consensus, based on the latest evidence-based medical data, provides guidance on the standardized application and safety management of PARP inhibitors in breast cancer treatment, aiming to serve as a reference for clinical practice.
    Journal • BRCA Biomarker • PARP Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)
    |
    BRCA2 mutation • BRCA1 mutation
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    Lynparza (olaparib) • AiRuiYi (fluzoparib)
    2d
    Inhibition of LncRNA THUMPD3-AS1 enhances olaparib-induced autophagy in BRCA mutant ovarian cancer cells via PI3K pathway. (PubMed, Cell Signal)
    Animal experiment further confirmed that downregulating THUMPD3-AS1 enhanced olaparib sensitivity to hinder the in vivo growth of OC cells through inhibiting PI3K/AKT/mTOR pathway. Our research revealed THUMPD3-AS1 as a promising target for OC therapy.
    Journal • BRCA Biomarker • PARP Biomarker
    |
    BRCA (Breast cancer early onset)
    |
    BRCA mutation
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    Lynparza (olaparib)
    2d
    Synthesis and Preliminary Evaluation of the 211At-Labeled PARP Inhibitor [211At]Talazoparib as a Targeted Alpha-Particle Emitting Therapeutic. (PubMed, Mol Pharm)
    In recent years, derivatives of olaparib and rucaparib have been radiolabeled for noninvasive imaging of PARP1 expression and targeted radionuclide therapy of PARP-expressing tumors. Methods for the chiral separation of precursor permitted radiolabeling of [211At]talazoparib without the need for separation from its inactive 211At-labeled enantiomer after radiolabeling, and scaled-up production was optimized. [211At]talazoparib exhibited promising potential as a targeted radiotherapeutic, particularly for settings where locoregional administration is warranted.
    Journal • PARP Biomarker
    |
    PARP1 (Poly(ADP-Ribose) Polymerase 1)
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    FOLH1 positive
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    Lynparza (olaparib) • Talzenna (talazoparib) • Rubraca (rucaparib)
    4d
    Synthetic lethality between PBRM1 deficiency and PARP inhibitors: exploiting G2/M checkpoint arrest in colorectal cancer. (PubMed, Mol Med)
    PBRM1 loss confers selective hypersensitivity to PARP inhibitors, which intensify DNA-damage signaling, promote G2/M checkpoint arrest, trigger apoptosis, and induce stress-response genes such as CSRNP3. Although this effect appears context-dependent and was not observed uniformly across all PBRM1-/- models tested. These results support further evaluation of PBRM1 as a potential predictive biomarker in defined molecular contexts rather than as a universal marker of PARP inhibitor sensitivity.
    Journal • PARP Biomarker
    |
    PBRM1 (Polybromo 1) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2) • ANXA5 (Annexin A5)
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    Lynparza (olaparib) • Rubraca (rucaparib)
    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
    |
    HRD (Homologous Recombination Deficiency) • RAD51 (RAD51 Homolog A) • RAD21 (RAD21 Cohesin Complex Component)
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    Lynparza (olaparib)
    6d
    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
    |
    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
    STN1 upregulation promotes PARPi resistance in BRCA2-deficient cancer cells via replication fork protection and suppression of ssDNA gap formation. (PubMed, bioRxiv)
    We observe that overexpression of STN1 enhances Olaparib resistance in multiple BRCA2-deficient cell lines and alleviates DNA damage under replication stress...Taken together, these findings suggest that elevated STN1 levels can partially compensate for BRCA2 loss by stabilizing stalled replication forks and limiting ssDNA gap accumulation. Our study uncovers a STN1-dependent pathway of replication stress tolerance that promotes PARPi resistance independently of homologous recombination restoration, highlighting STN1 as a potential biomarker and mechanistic contributor to therapeutic resistance in BRCA2-mutated cancers.
    Journal • BRCA Biomarker • PARP Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51 (RAD51 Homolog A) • MRE11A (MRE11 homolog, double strand break repair nuclease)
    |
    BRCA2 mutation • BRCA1 mutation
    |
    Lynparza (olaparib)