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

Computational design of PARP-1 inhibitors: QSAR, molecular docking, virtual screening, ADMET, and molecular dynamics simulations for targeted drug development. (PubMed, SAR QSAR Environ Res) - "Molecular docking studies revealed that several new compounds exhibited strong interactions with key amino acids GLY 227A, MET 229A, PHE 230A, and TYR 246A within the PARP-1 active site, similar to those observed in reference inhibitors Olaparib and AZD2461. Then, the top-ranked compound's (3a) ligand-protein complex underwent a 200 ns molecular dynamics (MD) simulation, confirming stable binding and revealing a robust set of intermolecular interactions maintained under physiological conditions."

Journal • Oncology • Ovarian Cancer • Solid Tumor • BRCA1 • BRCA2 • HRD

HUDSON: Phase II Umbrella Study of Novel Anti-cancer Agents in Patients With NSCLC Who Progressed on an Anti-PD-1/PD-L1 Containing Therapy (clinicaltrials.gov) - P2 | N=527 | Active, not recruiting | Sponsor: AstraZeneca | Trial primary completion date: Sep 2026 ➔ Sep 2024

Biomarker • IO biomarker • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Synergistic mechanism of olaparib and cisplatin on breast cancer elucidated by network pharmacology (Nature) - "The KEGG pathway analysis revealed that Olaparib and cisplatin may affect breast cancer through platinum drug resistance and longevity regulating pathway. Furthermore, Olaparib combined with cisplatin downregulated the expression of caspase-3 and caspase-9 proteins and upregulated p53, PARP, and SIRT1 protein levels in MCF-7 cells. Functionally, the cooperative effect of Olaparib and cisplatin reduced the applied concentration of cisplatin and enhanced the anticancer effect, emphasizing the importance of combination therapy to overcome side effects and significantly improve the anticancer efficacy of cisplatin."

Preclinical • Breast Cancer

AACR: Olaparib and pembrolizumab combination shows early promise in molecularly selected, tumor-agnostic trial (MD Anderson Press Release) - P2 | N=300 | KEYLYNK-007 (NCT04123366) | Sponsor: Merck Sharp & Dohme LLC | "Combination demonstrated complete responses and partial responses in different cancer types, including those beyond the currently approved indications for these therapies...The combination of the PARP inhibitor olaparib and the PD-1 inhibitor pembrolizumab showed initial antitumor activity with no new safety signals in a molecularly matched, tumor-agnostic trial, particularly in patients with BRCA1/2 mutations, according to results from a Phase II trial led by researchers at The University of Texas MD Anderson Cancer Center...Data from the KEYLYNK-007 trial were presented today in the clinical trials plenary session...Eighteen patients had a complete response to this treatment as determined by radiological imaging, with 11 of them in the BRCA1/2 mutation subgroup. Responses were seen in multiple tumor types for which these therapies are not currently approved."

P2 data • Solid Tumor

Olaparib as a rescue treatment in platinum-refractory germ-cell tumors: the IGG-02 phase II trial. (PubMed, ESMO Open) - P2 | "Olaparib as a single agent demonstrated no activity in heavily pretreated GCT patients. Future studies with PARP inhibitors should be planned in less-pretreated GCT patients based on molecular analysis to support better patient selection."

Journal • P2 data • Genito-urinary Cancer • Germ Cell Tumors • Oncology • Solid Tumor • Testicular Cancer • BRCA1 • PPM1D

Comparison Study of the Safety Profile of Olaparib Versus Niraparib: Analysis of Real-World Data from EudraVigilance. (PubMed, Pharmaceuticals (Basel)) - " This study highlights significant differences in the safety profiles of olaparib and niraparib, with implications for clinical decision-making. Continuous monitoring and personalized management of ADRs are essential to optimize patient outcomes."

Journal • Real-world evidence • Acute Myelogenous Leukemia • Fatigue • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Interstitial Lung Disease • Leukemia • Myelodysplastic Syndrome • Oncology • Ovarian Cancer • Pain • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Thrombocytopenia

Can Focused Ultrasound Overcome the Failure of Chemotherapy in Treating Pediatric Diffuse Intrinsic Pontine Glioma Due to a Blood-Brain Barrier Obstacle? (PubMed, Pharmaceuticals (Basel)) - "A patient-derived xenograft DIPG model exposed to high-intensity focalized ultrasound (HIFU) or low-intensity focalized ultrasound (LIFU) combined with MBs was treated with doxorubicin, panobinostat, olaparib, ONC201 (Dordaviprone®) and anti-PD1. This review reports pre-clinical and clinical studies performed to demonstrate the usefulness of FUS in patients with DIPG treated with some chemotherapy. The papers reviewed were published in PubMed until the end of 2024 and were found using a combination of the following keywords: diffuse intrinsic pontine glioma (DIPG), DIPG H3K27-altered, blood-brain barrier and BBB, focused ultrasound (FUS) and radiotherapy (RT)."

Journal • Review • Brain Cancer • CNS Disorders • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Diffuse Midline Glioma • Glioma • Oncology • Pediatrics • Solid Tumor

Recent Advances and Challenges in the Treatment of Advanced Pancreatic Cancer: An Update on Completed and Ongoing Clinical Trials. (PubMed, Cancers (Basel)) - "This includes adagrasib (a KRAS inhibitor), olaparib (a PARP inhibitor for BRCA mutations), APG-1387 (an IAP antagonist), minnelide (an anti-stromal agent), arimastat (an MMP inhibitor), MK-0646 (an IGF1R inhibitor), sirolimus (an mTOR inhibitor), and metabolic inhibitors. Furthermore, we have summarized novel approaches such as cancer vaccines and ablation techniques as emerging strategies in the treatment of advanced pancreatic cancer. We have also examined the challenges in treating advanced pancreatic cancer and the factors contributing to therapeutic failure, which may offer valuable insights for developing more effective treatment strategies and innovative drug designs."

Journal • Review • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • BRCA • KRAS

A first-in-class inhibitor of homologous recombination DNA repair counteracts tumour growth, metastasis and therapeutic resistance in pancreatic cancer. (PubMed, J Exp Clin Cancer Res) - "These findings underscore the great potential of BBIT20 as a novel multifaceted anticancer drug candidate for PDAC treatment."

IO biomarker • Journal • Fibrosis • Hepatology • Oncology • Ovarian Cancer • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • BARD1 • BRCA • BRCA1 • MIR20A • PD-L1 • RRM1 • SLC29A1

SOX5 inhibition overcomes PARP inhibitor resistance in BRCA-mutated breast and ovarian cancer. (PubMed, Cell Death Dis) - "This study identified SOX5 as a potential biomarker associated with PARP inhibitor resistance and addressed potential treatment strategies to overcome PARP inhibitor resistance using the olaparib-resistant preclinical model...Furthermore, the clinical relevance of SOX5 as a therapeutic target was supported by a significant association between SOX5 overexpression and poor prognosis in ovarian cancer on public mRNA microarray data sets. Therefore, we propose SOX5 as a promising therapeutic target for overcoming PARP inhibitor resistance in BRCA1/2-mutated breast and ovarian cancer."

Journal • Oncology • Ovarian Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2 • YAP1 • YBX1

Sustained clinical response to Olaparib in a patient with metastatic pancreatic cancer and somatic ATM-Mutation R2034Ter: a case report. (PubMed, Oncol Res Treat) - "Case Presentation A 77-year-old male patient with metastatic pancreatic ductal adenocarcinoma (PDAC) was initially treated with 5-fluoruracil, oxaliplatin and irinotecan, followed by 5-floururacil and irinotecan over the course of one year, leading to sustained partial remission...After developing one new liver metastasis at 21 months on Olaparib, he received conventional therapy with Gemcitabine/Cisplatin to which he responded. Conclusion This is the first case of a R2034Ter ATM mutant PDAC with sustained clinical response under Olaparib maintenance therapy reported. In select cases, ATM, a member of the BRCA pathway, might be a druggable target in pancreatic cancer."

Journal • Ataxia • Hepatology • Immunology • Movement Disorders • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Primary Immunodeficiency • Solid Tumor • ATM • BRCA • BRCA1 • BRCA2

Marine Sponge-Derived Gukulenin A Sensitizes Ovarian Cancer Cells to PARP Inhibition via Ferroptosis Induction. (PubMed, Mar Drugs) - "Resistance to PARP inhibitors (PARPi), such as olaparib (OLA), is a major challenge in ovarian cancer treatment...Additionally, GUA and OLA treatment suppressed ERK1/2 activation, and ERK overexpression attenuated the combination-induced cell death. Collectively, these findings suggest that marine-derived GUA enhances PARPi efficacy in ovarian cancer cells by inducing ferroptosis through oxidative stress and ERK pathway modulation."

Journal • Oncology • Ovarian Cancer • Solid Tumor

Dual-responsive nanoscale ultrasound contrast agent as an oxidative stress amplifier for enhanced DNA damage in BRCA-proficient ovarian cancer. (PubMed, Mater Today Bio) - "To potentiate the application of PARPi, an ultrasound contrast agent OLA-NDs for delivery of the PARPi olaparib (OLA) was established for enhancing DNA damage by blocking DNA repair...As a consequence, the combined application of UTMD and OLA-NDs demonstrated significant antitumor effects in vitro and in vivo. This combined strategy of amplifying oxidative damage improved lethality by promoting DNA DSBs and apoptosis with reduced adverse side effects, which would provide new insight for the clinical application of PARPi in BRCA-proficient ovarian cancer."

Journal • Metabolic Disorders • Oncology • Ovarian Cancer • Solid Tumor • BRCA • NOX4

Olaparib and Durvalumab in Patients with DNA Damage Repair Alterations and Biochemically Recurrent Prostate Cancer. (PubMed, J Immunother Precis Oncol) - No abstract available

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

management of an adrenal cortical carcinoma induced non-islet cell tumor hypoglycemia: a case report (ENDO 2025) - "She was started on adjuvant mitotane, and chemotherapy (cisplatin, etoposide, and doxorubicin) which induced cardiomyopathy...Osilodrostat was initiated for Cushing syndrome...Patient had recurrent severe hypoglycemic episodes, which were refractory to increasing carbohydrate intake, high-dose prednisone, and octreotide...She also received pasireotide 60mg and diazoxide 5mg/kg every 8 hours...Upon applying for alpelisib approval, her clinical status rapidly declined, and she died after 3 months of NITCH diagnosis...IGF2-mediated hypoglycemia was refractory to numerous therapeutic interventions, including paseriotide, pembrolizumab, olaparib, ivosidenib, and cabozantinib. This case emphasizes rare manifestations of metastatic ACC and limitations of existing medical therapies for NITCH.*. .*"

Case report • Clinical • Adrenal Cortex Carcinoma • Cardiomyopathy • Cardiovascular • Cushing’s Disease • Diabetes • Endocrine Disorders • Hematological Disorders • Hypoglycemia • Metabolic Disorders • Oncology • Pancreatic Cancer • Severe Hypoglycemia • Solid Tumor • IGF1 • IGF2

Prognosis stratification of patients with breast cancer based on disulfidptosis and ferroptosis. (PubMed, Medicine (Baltimore)) - "Furthermore, the high-risk group showed a higher tumor mutation burden compared to the low-risk group, which was also characterized by immune suppression and sensitivity to cisplatin, lapatinib and olaparib. Our study highlights the crucial role of disulfidptosis and ferroptosis in guiding clinical decision-making for patients with breast cancer, which also characterizes the intricate landscape of breast cancer and deepens our understanding of tumor heterogeneity."

Journal • Tumor mutational burden • Breast Cancer • Oncology • Solid Tumor • TMB

SPOP mutations increase PARP inhibitor sensitivity via CK2/PIAS1/SPOP axis in prostate cancer. (PubMed, JCI Insight) - "Moreover, an abnormal CK2/PIAS1/SPOP axis due to SPOP mutations or defects in CK2-mediated phosphorylation of PIAS1, as well as SPOP inhibitor treatment, led to impaired DDR, thus increasing olaparib-induced apoptosis of PCa cells and enhancing olaparib sensitivity in animal models and patient-derived organoids. This suggested that disruption of the CK2/PIAS1/SPOP signaling axis could serve as an indicator for targeted therapy of PCa using a PARP inhibitor."

Journal • Gene Therapies • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Targeted Protein Degradation • PIAS4 • SPOP

Novel APE1 endonuclease inhibitors as precision oncology therapeutics in high grade serous ovarian cancers discovered and developed from crystallography-based fragment library screening (AACR 2025) - "PARP1 inhibitor (Niraparib, Olaparib, Rucaparib) maintenance therapy improves progression-free survival in BRCA germline deficient ovarian cancer or platinum sensitive ovarian cancers. Olaparib and Talazoparib are approved for use in BRCA germ-line deficient breast cancers...Several compounds screened in MTS cell proliferation assay showed preferential cytotoxicity in PEO1 cells compared to PEO4 cells. Further cell based (clonogenics, 3D spheroids) and functional assays (DNA double strand break accumulation, cell cycle progression and apoptosis) are ongoing."

Breast Cancer • Epithelial Ovarian Cancer • Fallopian Tube Cancer • Genito-urinary Cancer • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Pancreatic Cancer • Peritoneal Cancer • Prostate Cancer • Solid Tumor • Triple Negative Breast Cancer • BRCA • BRCA1 • BRCA2 • HRD

Real-world outcomes among patients with metastatic castration-resistant prostate cancer (mCRPC) receiving guideline-recommended therapies after treatment with 177Lu-PSMA-617: A real-world prostate cancer disease observation (PRECISION) data platform analysis. (ASCO-GU 2025) - "Guideline-recommended therapies included abiraterone, enzalutamide, darolutamide, apalutamide, cabazitaxel, docetaxel, pembrolizumab, sipuleucel-T, niraparib, olaparib, talazoparib, rucaparib, and radium-223. In this real-world analysis, the majority of patients who received guideline-recommended therapies after 177Lu-PSMA-617 achieved at least a PSA50 response, suggesting that 177Lu-PSMA-617 treatment does not preclude response to other subsequent therapies."

Clinical • Metastases • Real-world • Real-world evidence • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Cost-Effectiveness Analysis of Olaparib and Niraparib With Abiraterone Versus Abiraterone for First-Line Treatment of BRCA Mutated Metastatic Castration-Resistant Prostate Cancer in Taiwan (ISPOR 2025) - "PROfound trial (second-line OLA vs abiraterone/enzalutamide) was then incorporated in the control arm through state transition model. Findings suggest that AAP is likely to be a cost-effective first-line treatment option for BRCA-mutated mCRPC from Taiwanperspective."

Clinical • Cost effectiveness • HEOR • Metastases • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • BRCA

Healthcare Resource Utilization (HCRU) and Costs of Poly(ADP-ribose) Polymerase Inhibitors (PARPi) as First-Line Maintenance (1LM) Treatment for Ovarian Cancer (OC) (ISPOR 2025) - "Key study inclusion criteria were ≥1 inpatient or ≥2 outpatient medical claims with an ICD-10-CM diagnosis code for ovarian, fallopian tube, or peritoneum cancer (collectively referred to as OC; January 1, 2017-June 30, 2022); initiated first-line (1L) platinum-based chemotherapy after the OC diagnosis; initiated 1LM PARPi monotherapy (niraparib, olaparib, or rucaparib) within 180 days of 1L platinum-based chemotherapy discontinuation (index date); and continuous enrollment during the 12 months preceding the OC diagnosis (baseline) through 30 days post-index. Results of this real-world analysis highlight that 1LM PARPi monotherapy use was associated with relatively low HCRU and mean medical costs in the 6 months after PARPi initiation."

Clinical • HEOR • Oncology • Ovarian Cancer • Solid Tumor

Early Access Program in oncology: Retrospective study at a Portuguese hospital (ECOP 2024) - "During the study period were submitted 163 EAP requests for abiraterone, amivantamab, bevacizumab, durvalumab, encorafenib, enfortumab, everolimus, erdafitinib, lenvatinib, lurbinectedin, niraparib, nivolumab, olaparib, pembrolizumab, pertuzumab, ramucirumab, sacituzumab govitecan, selpercatinib, trifluridine/tipiracil, trametinib+dabrafenib, trastuzumab-deruxtecan and tucatinib. Conclusion Most cases correspond to metastatic disease, EAPs facilitate timely access to innovative therapies for patients with high unmet medical needs. The majority of situations were financed, which confirms the importance of EAPs in an era where oncology is constantly innovating."

Retrospective data • Gastrointestinal Disorder • Oncology

Enhancing PARP inhibitor efficacy with CDK12/7/9 degradation in prostate cancer (AACR 2025) - "However, the development of castration-resistant prostate cancer (CRPC) and resistance to AR signaling inhibitors remains a significant clinical challenge.In recent years, the FDA has approved four PARP inhibitors (PARPis) - olaparib, rucaparib, talazoparib, and niraparib - either as monotherapy or in combination with AR signaling inhibitors for CRPC patients carrying deleterious germline or somatic BRCA1/2 mutations or other homologous recombination repair (HRR) gene mutations. In addition, BSJ-5-63 degrades CDK7/9, attenuating AR signaling and further promoting the synthetic lethality of PARP inhibition.Acute CDK12/7/9 degradation by BSJ-5-63 exhibits potent anti-tumor effects in both in vitro and in vivo CRPC models. This study introduces BSJ-5-63 as a promising therapeutic agent that targets both DNA repair and AR signaling pathways, offering potential benefits for a broad patient population."

Clinical • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • BRCA1 • BRCA2 • CDK12 • CDK7 • HRD

Secondary cytoreductive surgery for ovarian cancer recurrence and first-line maintenance therapy: A multicenter retrospective study. (PubMed, Eur J Obstet Gynecol Reprod Biol) - "Complete cytoreduction during secondary surgery for ovarian cancer recurrence is the strongest predictor of prognosis. First-line maintenance therapies do not appear to affect the safety and feasibility of secondary cytoreduction, although they may influence prognosis after secondary surgery."

Journal • Retrospective data • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

The impact of ethnicity on benefit from novel drugs approved for breast cancer treatment: a systematic review and meta-analysis of randomized phase 3 trials of the last decade. (SABCS 2024) - "23 phase III RCTs were identified in the aBC setting, with 1547 (11.1%) patients of Asian ethnicity. Experimental drugs tested included CDK4/6i (palbociclib, ribociclib, abemaciclib), SERD (elacestrant), PI3Ki (alpelisib), PARPi (olaparib, talazoparib), broad variety of anti-HER2 drugs (tucatinib, trastuzumab deruxtecan, pertuzumab, T-DM1, neratinib, margetuximab), anti-PD-1 and anti-PD-L1 drugs (pembrolizumab, atezolizumab) and anti-TROP2 drug (sacituzumab govitecan). 16 RCTs provided HR (95%CI) for PFS in the subgroup of Asians and 17 RCTs for Non-Asians."

IO biomarker • P3 data • Retrospective data • Review • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor