Lynparza (olaparib)

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.

Olaparib and temozolomide (OT) combination therapy is in clinical trial evaluation for rhabdomyosarcoma (RMS). The combination of OT + alpelisib also kills RMS cells which are resistant to standard-of-care combination chemotherapy and was effective in preclinical xenograft mouse models at curbing tumor growth. Our work defines a common resistance pathway in RMS and has credentialled PIK3CA/AKT inhibition as a preclinical strategy to kill therapy resistant RMS.

She showed a sustained clinical response to fourth-line treatment with the PARP inhibitor olaparib, which lasted 15 months and led to improved performance status. Subsequent progression led to combination therapy with atezolizumab and bevacizumab, maintaining stable disease for eight months. Molecularly guided treatment resulted in an overall survival of 25 months.

P1, N=28, Active, not recruiting, The Methodist Hospital Research Institute | Recruiting --> Active, not recruiting | Trial primary completion date: Sep 2025 --> Dec 2025

P2, N=462, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed

Our study demonstrated modest clinical benefits of D + O with ORR of 28.6% in subsets of heavily pretreated TNBC. Further detailed classification of DCs to understand the predictive role of DCs and prospective validation in a large cohort is required.

P1, N=10, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Oct 2025 --> Oct 2026

At a low 6 Gy X-ray dose, LSPA synergized with the PARP inhibitor Olaparib to induce extensive DNA damage... This theranostic strategy suppressed primary and distant (abscopal) tumors, prevented recurrence, and established durable immune memory with low-dose irradiation. Our findings present a clinically translatable approach that combines a nanosensitizer with PARP inhibition to turn immunologically "cold" tumors into "hot" ones, thereby enhancing the efficacy of low-dose radioimmunotherapy while limiting systemic toxicity.

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.

Although trabectedin-olaparib combination reached the prespecified threshold for statistical significance for PFS (p<0.10), the benefit was marginal in the all-comers STS population. Nonetheless, patients affected by PARP1-expressing STS and uterine leiomyosarcoma derived substantial benefit from the combination, supporting further histology- and biomarker-driven investigation in these settings.

PARPi are effective and generally with a manageable safety profile. However, secondary MDS and AML, though rare, remain serious adverse events with incompletely defined risk factors. The observed incidence, particularly with olaparib, is comparable to or higher than that reported in trials, though the sample size was limited. Close monitoring of hematologic AEs may be key to preventing these neoplasms.

The FDA has approved four PARP inhibitors (olaparib, rucaparib, niraparib, and talazoparib) for the treatment of ovarian, breast, prostate, and pancreatic cancer...The Chinese NMPA has approved three PARP antagonists (fuzuloparib, pamiparib, senaparib) for the treatment of ovarian cancer. All seven of these drugs are orally bioavailable and fall within the criteria of Lipinski's rule of five. Drug resistance develops in most PARP-inhibitor-treated cancer patients within one or two years.