Lynparza (olaparib) / Merck (MSD), AstraZeneca - LARVOL DELTA

New mechanistic insights into targeted protein degradation using Raman-active theranostic hydrophobic tags. (PubMed, Eur J Med Chem) - "By coupling our dual-purpose theranostic hydrophobic tags to the PARP inhibiting, anti-cancer therapeutic olaparib, we explore the degradation efficiency, mode of action and potency that these theranostics confer in ovarian cancer cells...Using SRS imaging, via the inherent Raman activity of the theranostic alkyne tag, we demonstrate involvement of the ER and autophagy after treatment with our drug conjugates. These results provide new insight into the mechanisms involved in HyT-induced protein degradation."

Journal • Oncology • Ovarian Cancer • Solid Tumor • Targeted Protein Degradation

PARP inhibitors and the rising incidence of secondary myelodysplastic syndrome and acute myeloid leukemia: A comprehensive meta-analysis (ASH 2025) - " The combined cohort included 106,793 patients treated with PARPi, including olaparib, niraparib, rucaparib, and talazoparib. This meta-analysis highlights that while MDS and AML are uncommon complications of PARP inhibitor therapy, their occurrence is clinically meaningful, with an overall incidence of approximately 1.5%. The risk notably increases with extended treatment duration and is associated with substantial mortality. These results underscore the importance of vigilant hematologic monitoring in patients receiving long-term PARP inhibitors and emphasize the need for prospective studies to discover predictive biomarkers and enhance personalized risk stratification."

Retrospective data • Acute Myelogenous Leukemia • Breast Cancer • Gynecologic Cancers • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Ovarian Cancer • Solid Tumor • BRCA

RPT1G, a novel hyperbolic NAMPT inhibitor, is highly effective against B-cell non-Hodgkin's lymphoma with germinal center origin (ASH 2025) - P1 | "RPT1G is efficacious in several hematological cancers, including acute leukemias andlymphomas. RPT1G is an effective treatment for NHL cancers of GC origin as a monotherapy and incombination with SOC and targeted therapies like olaparib. RPT1G was safe and well-tolerated in a first-in-human Phase 1 trial (NCT06667765) and is currently being evaluated in R/R AML and HR-MDS patients(NCT07107126)."

B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma • MYC • NAMPT

PARP1 facilitates transcriptional activity and stability of the BCL6 protein and is a therapeutic target in BCL6 expressing lymphomas (ASH 2025) - "While we showed that BCL6 is PARylated, BCL6 PARylation was not necessary for BCL6 TR,since reconstitution of PARP1 Crispr/Cas9-edited cells with wild type PARP1 or E988K PARP1 mutantsuppressed BCL6 reporter activity to levels observed in the non-manipulated 293T cells expressing BCL6.Since PARylation can regulate protein stability we performed cycloheximide (CHX) pulse-chaseexperiments showing progressive decrease in BCL6 protein levels over time, that was enhanced in thepresence of Olaparib and rescued by proteasome inhibitor MG132...Olaparib and Veliparib induced a pronounced decrease in colonyformation and cell viability as assessed by the MTS assay and potentiated similar effects of BCL6 inhibitor79-6. Both PARP1 inhibitors and BCL6 inhibitor 79-6 induced apoptosis and cell death in a cell line specificmanner. These combinations may be considered for clinical evaluation.Overall, for the first time our studies show that PARP1 plays an essential and direct role in..."

Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • BCL6 • MYC • PARP1

Hematologic toxicities associated with PARP inhibitors: Real world pharmacovigilance updated study using faers database with era-trend evaluation and serious outcome modeling (ASH 2025) - "We employed 4 PARPi drugs (included generic and brand names),olaparib, niraparib, rucaparib, and talazoparib were coded as a primary suspect drug. This is the largest real-world study to date demonstrating specific hematologic AEs withPARPi. Our results show distinct and varying patterns of hematologic toxicity across PARPi, with thestrongest disproportionality observed for cytopenias, particularly thrombocytopenia, leukopenia, andanemia, and notable signals for MDS. Recognizing these patterns will help clinicians better monitor andmanage patients receiving PARPi therapy."

Adverse events • Clinical • Real-world • Real-world evidence • Acute Myelogenous Leukemia • Breast Cancer • Leukopenia • Myelodysplastic Syndrome • Ovarian Cancer • Solid Tumor • Thrombocytopenia

The transition from myelodysplastic neoplasm to secondary acute myeloid leukemia is revealed by molecular analysis, while functional drug screening demonstrates novel sensitivity patterns with clinical implication (ASH 2025) - "There are only a limited number of agentsthat are FDA approved for treatment of MDS including BCL2 and IDH inhibitors, hypomethylating agents(HMAs), ESAs, luspatercept and imetelstat...For MDS patients, weidentified the most effective agents with the proportion of sensitive samples noted in parentheses:mitoxantrone (100%), olutasidenib (78%), venetoclax (67%), dinaciclib (67%), trametinib (67%), olaparib(56%), GSK3368715 (56%), pacritinib (44%), lenalidomide (44%), fludarabine (55%), tasquinimod (44%),veliparib (44%). For sAML patients, we identified lenalidomide, olutasidenib, GSK3368715 have high DSSsin all tested samples, while fludarabine, fedratinib, tasquinimod, trametinib, veliparib, mitoxantrone andolaparib have high DSSs in 75% of the AML samples...Cancer Research 2024), and our samples included SF3B1 and U2AF1 mutations.Summary This study of the transition of MDS to sAML highlights molecular changes and reveals new drugsensitivity with agents that could be..."

Biomarker • Clinical • IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • CD34 • FLT3 • JAK2 • NRAS • PTPN11 • SF3B1 • U2AF1

PARP inhibition by talazoparib results in leukemia cell death via induction of myeloid differentiation (ASH 2025) - "Across multiple cell lines, talazoparibconsistently exhibited more potent dose dependent anti-proliferative effects on AML growth than otherPARP inhibitors (olaparib,niraparib, rucaparib). We demonstrate here that talazoparib exerts potent anti-tumor activity across an array ofhuman AML cell lines, patient samples, and an in vivo xenograft model in part due to induction ofmyeloid differentiation. This was characterized by attenuated growth, prominent morphological andmolecular hallmarks, and increased cell death. Our results suggest that talazoparib may represent anovel mutation-agnostic differentiation therapy for acute myeloid leukemia."

Acute Myelogenous Leukemia • Breast Cancer • Hematological Malignancies • Leukemia • Ovarian Cancer • BRCA1 • BRCA2 • CD14 • CDK2 • IL1B • ITGAM

Inhibition of DOCK1 prevents the clonal expansion of high-risk TP53-mutant clonal hematopoiesis induced by genotoxic stressors. (ASH 2025) - "Our TP53-mutant human CH models faithfully recapitulates the clonal expansion ofTP53-mutant CH upon exposure to genotoxic stressors, including olaparib and paclitaxel. Further, weidentify DOCK1 as a potential SL partner with mutant TP53 demonstrating that inhibition of DOCK1 canprevent clonal expansion of TP53mut CH."

Hematological Malignancies • DOCK1 • TP53

Reduction of cell viability by immune-checkpoint inhibitor in co-cultured organoids derived from high-risk endometrial cancer patients pretreated with PARP inhibitor (ESMO Asia 2025) - P1 | "Patient-derived organoids (PDOs) from their hysterectomy specimens were co-cultured with autologous peripheral blood mononuclear cells (n=15), treated with pembrolizumab for three days, and cell viability was measured by ATP luciferase assay. 4/12 patients (33.3%) had low RAD51 score at baseline. This preliminary report showed that olaparib reduced HRR and induced DNA damage in EC tumors. The addition of ICI reduced cell viability in PDO co-cultured models. Further immune analyses are ongoing."

Checkpoint inhibition • Endometrial Cancer • Microsatellite Instability • Oncology • Solid Tumor • HRD • MSI • RAD51 • TP53

Prognostic impact of tumor immune features in BRCA pathogenic variant-positive breast cancer (ESMO Asia 2025) - "Background: Drug therapy for breast cancer harboring pathogenic BRCA variants (BRCA-PSVs) has entered a new era with the clinical implementation of olaparib... In BRCA-PSV positive breast cancer, local immune parameters, with a focus on CD8+ T cell infiltration, represent more robust prognostic indicators than systemic immune indices. The paradoxical association between low TIL levels and favorable survival outcomes suggests that the functional composition of TILs, the presence of an immunosuppressive tumor microenvironment, and mechanisms of immune evasion may play pivotal roles. These findings support the necessity of comprehensive multiparametric immune profiling that integrates spatial, phenotypic, and functional analyses to refine prognostication and guide the development of tailored immunotherapeutic strategies."

IO biomarker • Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA • CD8

Impact of PARP inhibitor resistance on subsequent treatment outcomes and platinum sensitivity in advanced ovarian cancer: Insights from the National University Cancer Institute, Singapore (ESMO Asia 2025) - "This analysis included those who received 1L or second-line and beyond (≥2L) PARPi maintenance—Olaparib, Niraparib, or Rucaparib—between May 2020 and November 2024. Progression on PARPi in advanced OC correlates with reduced efficacy of subsequent therapies and high rates of platinum resistance. These findings emphasize the urgent need for novel, effective treatment strategies after PARPi failure to improve pt outcomes."

Clinical • Metastases • Oncology • Ovarian Cancer • Solid Tumor • BRCA • HRD

Safety and efficacy of PARP inhibitors in metastatic castration-resistant prostate cancer with DNA damage repair alterations: A systematic review and meta-analysis of randomized controlled trials (ESMO Asia 2025) - "Risk of bias was assessed with Cochrane RoB 2.0. Seven RCTs evaluating olaparib, niraparib, rucaparib, and talazoparib in DDR-altered mCRPC were included. PARP inhibitors significantly prolong rPFS and improve OS in DDR-altered mCRPC, especially in BRCA1/2-mutated disease. However, this comes with an increased risk of SAEs, particularly hematologic events. These findings underscore the importance of individualized risk–benefit assessment, close monitoring, and judicious use of PARP inhibitors in routine practice for biomarker-selected mCRPC patients."

Metastases • Retrospective data • Review • Acute Myelogenous Leukemia • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Prostate Cancer • Solid Tumor • BRCA1 • BRCA2

PROspect: A multi-center, single-arm, prospective study to investigate the efficacy and safety of olaparib monotherapy in newly diagnosed mCRPC patients who progressed on NHA with HRR gene mutation (ESMO Asia 2025) - "Olaparib showed promising efficacy and an acceptable safety profile in post-NHA 1L mCRPC patients with HRR (especially BRCA) mutation."

Clinical • Monotherapy • Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • BARD1 • BRCA • BRCA1 • BRCA2 • BRIP1 • CDK12 • CHEK1 • CHEK2 • FANCL • HRD • PALB2 • RAD51B • RAD51C • RAD51D • RAD54L

Real-world treatment patterns and safety of olaparib in Chinese patients with prostate cancer: A multicenter, prospective, real-world study (DIM study) (ESMO Asia 2025) - P | "54 (90%) pts had NHA exposure while 27 (45%) had docetaxel exposure before initiating olaparib. This real-world analysis indicates that a considerable proportion of prostate cancer pts are receiving several lines of therapy prior to olaparib. Olaparib was well tolerated in real-world clinical practice in China and its safety profile was consistent with previous reports."

Clinical • HEOR • Real-world • Real-world evidence • Acute Myelogenous Leukemia • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Prostate Cancer • Solid Tumor • BRCA

Clinicogenomic profile, treatment patterns, and outcomes of BRCA-mutated cancers: Real-world data from western India (ESMO Asia 2025) - "Among BRCA-positive, 35.4% (93/263) received PARPi mainly olaparib (81.7%) rucaparib (18.3%) with 11/93 breast cancer patients treated adjuvantly; ORR was 90.5% for metastatic breast cancer & 88.9% for ovarian cancer. BRCA mutations serve as key therapeutic targets in ovarian and breast cancers; advancement in testing and expanded PARP inhibitor access have markedly enhanced clinical outcomes."

Clinical • Real-world • Real-world evidence • Breast Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2 • TP53

MAGED1 (NRAGE) inhibition enhances sensitivity to PARP inhibitors in BRCA-mutated breast cancer cell lines (ESMO Asia 2025) - "Cell viability was assessed by CytoFLEX after treatment with drugs (cisplatin, olaparib and niraparib) at several concentrations (0–300 μM) in Hs578T, HCC-1937 (BRCA1 5382insC), and BT-474 (BRCA2 c.0391C>A) breast cancer cell lines. Our study demonstrates that silencing of MAGED1 enhances sensitivity to PARP inhibitors in BRCA1/2-mutant breast cancer cell lines. These results suggest that MAGED1 is involved in HRD and could be a therapeutic target to enhance PARP inhibitor response in breast cancer."

Preclinical • Breast Cancer • Melanoma • Oncology • Solid Tumor • Triple Negative Breast Cancer • BARD1 • BRCA • BRCA1 • BRCA2 • HRD • RAD51 • RNF8

MULTISARC: Molecular Profiling of Advanced Soft-tissue Sarcomas (clinicaltrials.gov) - P3 | N=603 | Active, not recruiting | Sponsor: Institut National de la Santé Et de la Recherche Médicale, France | Trial completion date: Oct 2025 ➔ Jan 2026

IO biomarker • Trial completion date • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Durvalumab with carboplatin/paclitaxel and bevacizumab followed by durvalumab and bevacizumab with or without olaparib maintenance in newly diagnosed non-BRCA-mutated advanced ovarian cancer. (PubMed, Ann Oncol) - P3 | "DUO-O met its primary PFS endpoints for first-line durvalumab plus carboplatin/paclitaxel and bevacizumab followed by durvalumab, bevacizumab plus olaparib maintenance versus carboplatin/paclitaxel and bevacizumab followed by bevacizumab in the non-tBRCAm HRD-positive and non-tBRCAm ITT populations. Further insight into long-term benefit is anticipated with additional follow-up."

Journal • Oncology • Ovarian Cancer • Solid Tumor • BRCA • HRD

Olaparib has synergistic effects with DNA damaging agents in pancreatic ductal adenocarcinoma. (PubMed, Biochem Biophys Res Commun) - "The synergistic effects observed in PDAC cancer cells when combining the PARP inhibitor, olaparib, with the DNA damaging agents, doxorubicin and mitoxantrone, provide a preclinical rationale for considering this combination as a potential therapeutic approach in PDAC patients."

Journal • Gene Therapies • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

Olaparib in the Treatment of BRCA1/2 Unmutated and BRCA1 Promoter Methylated Recurrent and Metastatic Triple-negative Breast Cancer (clinicaltrials.gov) - P2 | N=30 | Not yet recruiting | Sponsor: Hebei Medical University Fourth Hospital | Trial completion date: Sep 2024 ➔ Sep 2031 | Trial primary completion date: Sep 2023 ➔ Sep 2030

Trial completion date • Trial primary completion date • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BRCA1 • BRCA2 • ER • HER-2 • PGR

Phase II study of durvalumab plus olaparib in patients with metastatic pancreatic cancer and DNA damage repair genes alterations. (ASCO-GI 2026) - P2 | "Funded by AstraZeneca Clinical Trial Registration Number: NCT05659914 The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Clinical • Metastases • P2 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Dual Inhibition of PARP and Akt Induces Metabolic Collapse and Apoptosis in Breast Cancer Cells. (PubMed, Cancers (Basel)) - "These findings indicate that the combination of olaparib and capivasterib is a promising therapeutic strategy for breast cancer. Furthermore, evaluation of in vivo toxicity and antitumor effectiveness is essential to validate its potential."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

SLX1 Inhibition Enhances Olaparib Sensitivity by Impairing Homologous Recombination Repair in Breast Cancer. (PubMed, Int J Mol Sci) - "In vivo, SLX1 knockdown synergizes with Olaparib to suppress tumor growth in xenograft models. These findings establish SLX1 as a critical regulator of HR function in BRCA1-proficient breast cancer and a promising target for restoring PARP inhibitor sensitivity through induced HR deficiency."

Journal • Breast Cancer • Oncology • Solid Tumor • BRCA1 • HRD • RAD51

Omics and artificial intelligence integration for stratifying blast crisis CML using COSMIC signatures and pan-cancer precision drug repurposing. (PubMed, World J Clin Oncol) - "This WES-AI-ML framework provides mutation-guided therapies for BC-CML, enabling real-time stratification and Food and Drug Administration-approved drug repurposing. While this exploratory study is limited by its small sample size (n = 7), it establishes a methodological framework for precision oncology stratification that warrants validation in larger, multi-center cohorts."

Journal • Pan tumor • Tumor mutational burden • Breast Cancer • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • BCR • BRCA2 • CSF3R • TMB • TP53

Comparative analysis of molecular targeted radiosensitizers in 2D and 3D cancer cell line models. (PubMed, Acta Oncol) - "Integrating multiple culture models enhances the detection of cell line - and drug-specific radiosensitization. Although 2D and 3D cultures produced largely similar results, and 2D assays provide a practical alternative when 3D methods are not feasible, the 3D cultures reveal additional ECM-dependent responses. These results emphasize the utility of physiologically relevant platforms for robust screening and prioritization of candidate radiosensitizers."

Clinical • Journal • Preclinical • Lung Cancer • Oncology • Solid Tumor