Lynparza (olaparib)

Third, co-administration of the PARP inhibitor olaparib (Ola) functionally impairs PARP-mediated DNA repair, thereby converting RDT-induced DNA lesions into lethal damage and promoting apoptosis. Guided by its intrinsic computed tomography-mediated visibility, which revealed peak tumor accumulation at 12 h post-administration, the triple‑combination regimen achieved 85.5% tumor suppression in an orthotopic triple-negative breast cancer model without evident toxicity. This study presents a strategic framework for an intelligent nanoplatform capable of converting low-dose physical energy into biological cascades, thereby systematically disrupting parallel tumor defense mechanisms and broadening the therapeutic scope of radiotherapy.

P1, N=26, Terminated, Repare Therapeutics | Trial completion date: Dec 2028 --> Oct 2025 | Active, not recruiting --> Terminated | Trial primary completion date: Oct 2026 --> Oct 2025; Sponsor decided to terminate study early

P2, N=1376, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: May 2026 --> Jan 2027

Together, we identify hotspots of deleterious RAD51D variants and uncover the mechanisms by which variants compromise its biochemical functions. Used a multiplexed assay of functional effect (MAVE) to assess the functionality via olaparib sensitivity of 6,888 RAD51D coding variants, which can be used for variant classification Provided cellular functional analysis for 70 clinically-identified breast and ovarian cancer RAD51D variants Identified key regions and enzymatic activities of RAD51D critical for its function in the BCDX2 and the X3CDX2 complexesDetermined mechanism of RAD51D-mediated regulation of BCDX2 ATPase activity.

In recurrent ovarian cancer, niraparib+pembrolizumab showed modest activity with durable responses in homologous recombination-deficient (HRD) tumors; olaparib+durvalumab demonstrated high activity in gBRCA platinum-sensitive relapse, and adding bevacizumab broadened benefit in non-BRCA cohorts. In the newly diagnosed disease, rucaparib+nivolumab maintenance failed to improve PFS versus rucaparib alone. Endometrial trials (olaparib+durvalumab; talazoparib+avelumab in mismatch repair-proficient disease) showed limited activity overall, with signals restricted to biomarker-selected subgroups...PARP+PD-1/PD-L1 combinations are most compelling in ovarian cancer, particularly in BRCA/HRD tumors and, in selected settings, with the addition of bevacizumab, while frontline maintenance benefit remains unproven and endometrial activity is modest. Biomarker-guided selection, rational triplets with non-cytotoxic partners, and optimized sequencing warrant further evaluation.

Olaparib met the prespecified criteria to declare a signal of activity in patients with ATM-altered cancer within the LC and HP cohorts but not the CRC or PC cohorts.

Syrosingopine treatment sensitizes LUAD cells to PARP inhibitor (PARPi) and potentiates the therapeutic efficacy of olaparib in a mouse LUAD model. Altogether, our study reveals that lactylation drives RIG-I nuclear function to inhibit DNA damage repair via PARP suppression. This supports the potential co-administration of syrosingopine and PARPi for LUAD treatment.

BRCArev can emerge in PCA in the absence of prior PARPi therapy, particularly following exposure to cytotoxic chemotherapy and radiation. These findings support that DNA-damaging therapies may promote BRCArev formation, potentially predisposing to primary PARPi resistance. Early integration of PARPi therapy before chemotherapy may enhance clinical benefit and circumvent emergence of primary resistance.

Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and β-catenin expression suggested decrease apoptosis within tumour tissue. Both 3-aminobenzamide (20 mg/kg; i.p.) and Olaparib (10 mg/kg; orally) exhibited coloprotective effects by modulating PARP-1-NLRP3 inflammasome and autophagy pathways in a model of colitis-associated colorectal cancer.

P2, N=96, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

Notably, silencing EME1 significantly increased the sensitivity of NPC cell lines to CPT by enhancing ATM-CHEK2 phosphorylation and inducing nuclear abnormalities. Collectively, our findings suggest that combining EME1 modulation with agents such as CPT or olaparib could be an effective treatment strategy for NPC patients.

In vitro, niraparib lacks any CYP inhibition, induces CYP1A2 but not CYP3A4, and is not a CYP substrate, unlike some other PARPi's, which inhibit and induce numerous enzymes/transporters and are objects of CYP metabolism. At clinically relevant doses of niraparib ≥ 200 mg, a weak induction risk is predicted with sensitive CYP1A2 substrates, such as caffeine, and both niraparib and olaparib clinically increase serum creatinine in cancer patients, with up to a moderate inhibition risk predicted with MATE-1/-2K substrates, such as metformin, using a PBPK model of niraparib in the absence of a dedicated DDI study.