Olaparib
Olaparib is a small-molecule inhibitor of poly(ADP-ribose) polymerase (PARP), marketed as Lynparza and developed under the codes AZD2281 and KU59436.
Olaparib is a small-molecule inhibitor of poly(ADP-ribose) polymerase (PARP), marketed as Lynparza and developed under the codes AZD2281 and KU59436. It is an orally administered targeted anticancer drug, used both as maintenance therapy after platinum-based chemotherapy and in combination regimens across ovarian, breast, prostate and pancreatic cancers.
The drug binds the catalytic site of PARP1 and the related enzyme PARP2, blocking the poly(ADP-ribosyl)ation that recruits repair factors to single-strand breaks, and — more consequentially — traps the enzyme on the DNA it has bound. A trapped PARP is a worse lesion than an absent one: the stalled complex collapses the oncoming replication fork into a double-strand break that is particularly dependent on homologous recombination for accurate repair. Tumors deficient in that pathway, most characteristically those with germline or somatic pathogenic variants in BRCA1 or BRCA2 and more broadly those scored as homologous recombination deficiency (HRD)-positive, cannot compensate, so the drug is selectively lethal to them while sparing repair-proficient tissue. This synthetic-lethal relationship underlies both its indications and the use of BRCA testing as a companion diagnostic.
The same dependence on the DNA damage response explains its use alongside DNA-damaging and antiangiogenic agents — the platinum drugs cisplatin and carboplatin, taxanes such as paclitaxel, temozolomide, radiotherapy and bevacizumab — and its pairing in prostate cancer with abiraterone plus prednisone or prednisolone, a regimen established in trials, unlike combination with enzalutamide. It is also combined with immune checkpoint blockade such as the anti-PD-L1 antibody durvalumab. Resistance arises through reversion mutations that restore homologous recombination, loss of the trapping-sensitive target, drug efflux via p-glycoprotein, restored fork protection, and adaptive responses including autophagy; response has been inconsistent in tumors that appear PARP-inhibitor-sensitive on other grounds, such as Ewing sarcoma. Common toxicities — myelosuppression, fatigue and gastrointestinal effects — reflect action on proliferating tissue, and prolonged exposure carries a small risk of myelodysplastic syndrome or acute myeloid leukemia.
Where the papers sit
25 papers from the last 6 months study olaparib directly · updated from PubMed 12 Oct 2026
Study type 4 clinical trials · 5 observational · 2 human data · 13 preclinical · 1 unclassified
Themes 4 themes · 1 paradigm shift · 1 new direction
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PARP Inhibition in Ovarian Cancer
BRCA-mutated advanced ovarian cancer is moving toward first-line olaparib maintenance, with progression-free survival as the main clinical endpoint. Real-world studies reinforce benefit while highlighting severe anemia as a management concern. Resistance is being linked to drug-specific DNA-repair mechanisms, prompting interest in PARP1-targeted conjugates and other combinations. Cost-effectiveness and integration with bevacizumab or immunotherapy remain open questions.
10 papers · 40%
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DNA Repair and PARP Sensitivity
DNA-repair defects are being used to identify tumors vulnerable to PARP inhibition across several cancer types. The work increasingly tests olaparib with chemotherapy, immunotherapy or pathway-directed agents, including disruption of G4-STAT1 signaling. Autophagy is a recurring mechanism that weakens PARP inhibitor sensitivity, while genomic profiling seeks actionable repair abnormalities. Biomarker selection and the durability of these combinations remain unresolved.
6 papers · 24%
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PARP Therapy in Prostate Cancer
BRCA1/2 and other homologous-recombination defects are guiding olaparib use in metastatic prostate cancer. Real-world outcomes focus on treatment patterns, genetic testing, progression-free survival and anemia. Combination with abiraterone is being explored earlier, in metastatic hormone-sensitive disease, rather than limiting PARP inhibition to castration-resistant cancer. Comparisons with enzalutamide and radioligand therapy emphasize both positioning and safety.
5 papers · 20%
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PARP Inhibition in Triple-Negative Breast Cancer
Triple-negative breast cancer treatment is moving toward biomarker-selected PARP inhibition based on BRCA and broader homologous-recombination deficiency. Real-world studies are assessing uptake of germline BRCA testing as a companion diagnostic, alongside outcomes in metastatic disease. USP1 inhibition is emerging as a combination strategy to strengthen PARP inhibitor activity. The relative value of germline testing, non-germline repair defects and other targets such as SYK remains under study.
4 papers · 16%
Olaparib response is not determined solely by DNA-repair vulnerability because non-HRR resistance mechanisms can independently defeat it
The Ewing sarcoma cell study and the ovarian-cancer resistance study assumed that olaparib’s activity could be understood primarily through PARP inhibition and the tumor’s DNA-repair status, but they instead identify distinct non-HRR routes to treatment failure: autophagy impairs PARP-inhibitor sensitivity in Ewing sarcoma, while P-glycoprotein/ABCB1 contributes to olaparib resistance in ovarian cancer 42215796May 41998207Apr. The resulting change is that HRR or related DNA-repair biomarkers cannot be treated as sufficient explanations of response; autophagy and drug efflux must also be considered when predicting or overcoming olaparib resistance.
Olaparib is repurposed as a blood-brain-barrier-targeted conjugate for glioblastoma
The glioblastoma in-vitro study assumed that the principal limitation of olaparib in brain tumors was inadequate delivery across the blood–brain barrier, and instead used olaparib conjugated to a heptamethine cyanine dye to promote cellular uptake while retaining PARP1 inhibition 42035252Apr. This gives olaparib a role beyond conventional systemic PARP-inhibitor treatment: it becomes the active component of a brain-directed delivery construct, creating a therapeutic route for glioblastoma that the other studies do not use.
Papers
The 25 papers from the last 6 months that study olaparib directly, newest first, by theme and by study type. Study types come from PubMed publication types and MeSH headings.
By theme
PARP Inhibition in Ovarian Cancer (10)
- Chemotherapy with or without pembrolizumab followed by maintenance pembrolizumab with or without olaparib as first-line treatment of patients with advanced BRCA non-mutated epithelial ovarian cancer (ENGOT-OV43/GOG-3036/KEYLYNK-001): a randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet. Oncology · 7 Sept 2026 PMID 42705254
- Olaparib as the first-line maintenance therapy in advanced-stage epithelial ovarian cancer patients with BRCA mutations - Real-world experience from Taiwan. Taiwanese journal of obstetrics & gynecology · 25 Aug 2026 PMID 42642151
- Cost-Effectiveness of olaparib plus bevacizumab versus bevacizumab monotherapy as first-line maintenance for patients with advanced ovarian cancer: a analysis from a Chinese healthcare perspective. Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 22 Jul 2026 PMID 42484750
- An integrated in silico and SPR-based workflow identifies FDA-approved drugs as previously unrecognized SIRT3 binders. Bioorganic chemistry · 14 Jul 2026 PMID 42447746
- Molecular Boomerangs Against Cancer: Design, Synthesis, Biological Evaluation, and In Silico Study of Novel Dual PARP-1/EGFR Inhibitors. Drug development research · 28 May 2026 PMID 42207930
- Severe anemia as a risk factor in Japanese patients with ovarian cancer receiving olaparib: a retrospective study. BMC cancer · 8 May 2026 PMID 42104280
- Synergistic antitumor effect between Olaparib and Chidamide by regulation of MYBL2 in lung cancer. Anti-cancer drugs · 2 May 2026 PMID 42068974
- In Vitro Evaluation of PARP1 Inhibitor Olaparib-Cyanine Dye Conjugate for the Treatment of Glioblastoma. ChemMedChem · 26 Apr 2026 PMID 42035252
- Identification of novel drug-specific PARP inhibitor resistance mechanisms in ovarian cancer-implications for clinical practice. British journal of cancer · 17 Apr 2026 PMID 41998207
- Application of PARP1-Specific Pt(II)-Based Targeted Drug Conjugate in the Treatment of Ovarian Cancer by Inhibiting PARP1 and Suppressing DNA Damage Repair. Inorganic chemistry · 17 Apr 2026 PMID 41996568
DNA Repair and PARP Sensitivity (6)
- DNA hypomethylation identifying clinical benefit subgroup of small-cell lung cancer: multi-omics analysis of a phase II trial with durvalumab plus olaparib as maintenance therapy. Journal for immunotherapy of cancer · 14 Aug 2026 PMID 42601174
- Genomic profiling identifies actionable DNA-repair defects in a new cervical cancer model. Scientific reports · 29 Jul 2026 PMID 42527451
- Downregulation of SLC44A4 in nasopharyngeal carcinoma is associated with malignant progression, B-cell/TLS-related immune features, and sensitivity to DNA-damaging agents. PloS one · 26 Jun 2026 PMID 42361082
- Electroporation as a strategy to improve the efficacy of chemotherapy in neuroblastoma: an in vitro study. Radiology and oncology · 26 Jun 2026 PMID 42359758
- Autophagy impairs the sensitivity of Ewing sarcoma cells to PARP inhibitors. Cancer chemotherapy and pharmacology · 29 May 2026 PMID 42215796
- A small molecule disrupts G4-STAT1 interaction and synergizes with olaparib to drive cancer cell death. Nucleic acids research · 6 May 2026 PMID 42087785
PARP Therapy in Prostate Cancer (5)
- Real-World Outcomes of Olaparib in Japanese Patients With BRCA-Mutated Metastatic Castration-Resistant Prostate Cancer: Exploratory Analysis of BRCA2 Loss and Microsatellite Instability Status. International journal of urology : official journal of the Japanese Urological Association · 28 Aug 2026 PMID 42661511
- Development of a stability-indicating RP-UPLC method for simultaneous determination of Abemaciclib and Olaparib with LC-MS characterization of degradation products and in vitro performance evaluation. Journal of chromatographic science · 23 Jul 2026 PMID 42490602
- Comparative safety profiles of enzalutamide, olaparib, and lutetium Lu-177 vipivotide tetraxetan in patients with prostate cancer: a real-world disproportionality analysis of the FAERS database. World journal of urology · 14 Jul 2026 PMID 42446704
- Real-world clinical outcomes, genetic testing patterns, and treatment patterns of patients with metastatic castration-resistant prostate cancer treated with olaparib monotherapy in the United States. Urologic oncology · 10 Jul 2026 PMID 42431822
- Olaparib combined with abiraterone in HRR-mutated metastatic hormone-sensitive prostate cancer: a single-arm phase II trial. World journal of urology · 11 May 2026 PMID 42115448
PARP Inhibition in Triple-Negative Breast Cancer (4)
- Olaparib in HR-deficient, metastatic triple-negative breast and platinum-sensitive relapsed ovarian cancers without germline mutations in BRCA1/2: phase 2 EMBRACE trial. British journal of cancer · 8 Jul 2026 PMID 42420629
- Integrating Machine Learning and Structure-Guided Discovery of a Novel Type II SYK Inhibitor for Treating Triple-Negative Breast Cancer. Journal of medicinal chemistry · 17 Jun 2026 PMID 42304805
- Real-world uptake of gBRCA testing as a companion diagnostic for olaparib in patients with high-risk HER2-negative early breast cancer in Japan: a cross-sectional multicenter study (BRCAwareness). Breast cancer (Tokyo, Japan) · 23 May 2026 PMID 42176176
- Design and Synthesis of USP1 Inhibitors: Synergistic Antitumor Activity with PARP Inhibitors in Triple-Negative Breast Cancer. Journal of medicinal chemistry · 29 Apr 2026 PMID 42054575
By study type
Clinical trials (4)
- Chemotherapy with or without pembrolizumab followed by maintenance pembrolizumab with or without olaparib as first-line treatment of patients with advanced BRCA non-mutated epithelial ovarian cancer (ENGOT-OV43/GOG-3036/KEYLYNK-001): a randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet. Oncology · 7 Sept 2026 PMID 42705254
- DNA hypomethylation identifying clinical benefit subgroup of small-cell lung cancer: multi-omics analysis of a phase II trial with durvalumab plus olaparib as maintenance therapy. Journal for immunotherapy of cancer · 14 Aug 2026 PMID 42601174
- Olaparib in HR-deficient, metastatic triple-negative breast and platinum-sensitive relapsed ovarian cancers without germline mutations in BRCA1/2: phase 2 EMBRACE trial. British journal of cancer · 8 Jul 2026 PMID 42420629
- Olaparib combined with abiraterone in HRR-mutated metastatic hormone-sensitive prostate cancer: a single-arm phase II trial. World journal of urology · 11 May 2026 PMID 42115448
Observational studies and case reports (5)
- Real-World Outcomes of Olaparib in Japanese Patients With BRCA-Mutated Metastatic Castration-Resistant Prostate Cancer: Exploratory Analysis of BRCA2 Loss and Microsatellite Instability Status. International journal of urology : official journal of the Japanese Urological Association · 28 Aug 2026 PMID 42661511
- Olaparib as the first-line maintenance therapy in advanced-stage epithelial ovarian cancer patients with BRCA mutations - Real-world experience from Taiwan. Taiwanese journal of obstetrics & gynecology · 25 Aug 2026 PMID 42642151
- Comparative safety profiles of enzalutamide, olaparib, and lutetium Lu-177 vipivotide tetraxetan in patients with prostate cancer: a real-world disproportionality analysis of the FAERS database. World journal of urology · 14 Jul 2026 PMID 42446704
- Real-world clinical outcomes, genetic testing patterns, and treatment patterns of patients with metastatic castration-resistant prostate cancer treated with olaparib monotherapy in the United States. Urologic oncology · 10 Jul 2026 PMID 42431822
- Real-world uptake of gBRCA testing as a companion diagnostic for olaparib in patients with high-risk HER2-negative early breast cancer in Japan: a cross-sectional multicenter study (BRCAwareness). Breast cancer (Tokyo, Japan) · 23 May 2026 PMID 42176176
Human data, design not indexed (2)
- Cost-Effectiveness of olaparib plus bevacizumab versus bevacizumab monotherapy as first-line maintenance for patients with advanced ovarian cancer: a analysis from a Chinese healthcare perspective. Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 22 Jul 2026 PMID 42484750
- An integrated in silico and SPR-based workflow identifies FDA-approved drugs as previously unrecognized SIRT3 binders. Bioorganic chemistry · 14 Jul 2026 PMID 42447746
Preclinical: animal, cell and lab studies (13)
- Genomic profiling identifies actionable DNA-repair defects in a new cervical cancer model. Scientific reports · 29 Jul 2026 PMID 42527451
- Development of a stability-indicating RP-UPLC method for simultaneous determination of Abemaciclib and Olaparib with LC-MS characterization of degradation products and in vitro performance evaluation. Journal of chromatographic science · 23 Jul 2026 PMID 42490602
- Downregulation of SLC44A4 in nasopharyngeal carcinoma is associated with malignant progression, B-cell/TLS-related immune features, and sensitivity to DNA-damaging agents. PloS one · 26 Jun 2026 PMID 42361082
- Electroporation as a strategy to improve the efficacy of chemotherapy in neuroblastoma: an in vitro study. Radiology and oncology · 26 Jun 2026 PMID 42359758
- Integrating Machine Learning and Structure-Guided Discovery of a Novel Type II SYK Inhibitor for Treating Triple-Negative Breast Cancer. Journal of medicinal chemistry · 17 Jun 2026 PMID 42304805
- Autophagy impairs the sensitivity of Ewing sarcoma cells to PARP inhibitors. Cancer chemotherapy and pharmacology · 29 May 2026 PMID 42215796
- Molecular Boomerangs Against Cancer: Design, Synthesis, Biological Evaluation, and In Silico Study of Novel Dual PARP-1/EGFR Inhibitors. Drug development research · 28 May 2026 PMID 42207930
- A small molecule disrupts G4-STAT1 interaction and synergizes with olaparib to drive cancer cell death. Nucleic acids research · 6 May 2026 PMID 42087785
- Synergistic antitumor effect between Olaparib and Chidamide by regulation of MYBL2 in lung cancer. Anti-cancer drugs · 2 May 2026 PMID 42068974
- Design and Synthesis of USP1 Inhibitors: Synergistic Antitumor Activity with PARP Inhibitors in Triple-Negative Breast Cancer. Journal of medicinal chemistry · 29 Apr 2026 PMID 42054575
- In Vitro Evaluation of PARP1 Inhibitor Olaparib-Cyanine Dye Conjugate for the Treatment of Glioblastoma. ChemMedChem · 26 Apr 2026 PMID 42035252
- Identification of novel drug-specific PARP inhibitor resistance mechanisms in ovarian cancer-implications for clinical practice. British journal of cancer · 17 Apr 2026 PMID 41998207
- Application of PARP1-Specific Pt(II)-Based Targeted Drug Conjugate in the Treatment of Ovarian Cancer by Inhibiting PARP1 and Suppressing DNA Damage Repair. Inorganic chemistry · 17 Apr 2026 PMID 41996568
Unclassified: not yet indexed with MeSH (1)
- Severe anemia as a risk factor in Japanese patients with ovarian cancer receiving olaparib: a retrospective study. BMC cancer · 8 May 2026 PMID 42104280
Written from 25 PubMed abstracts, each one listed by PMID above. Published: 2026-07-02. Last written: 2026-08-26 by GPT. Corrections: 2026-09-26 by GPT. Reviewed by a human editor on 2026-07-23. Drafted by language models from published abstracts; not medical advice.