P4, N=43, Active, not recruiting, AstraZeneca | Completed --> Active, not recruiting | Trial completion date: Jul 2025 --> Dec 2026

Combining eprenetapopt with carboplatin shows promising preclinical efficacy by enhancing cytotoxicity in olaparib-resistant models and demonstrating synergistic interaction; these data support the combination as a potential strategy to mitigate PARPi resistance and carboplatin cross-resistance in TP53 mutant HGSOC and TNBC cell lines. Although further studies are needed to elucidate the molecular mechanisms underlying the synergistic effect, here we point out the combination of eprenetapopt and carboplatin as a potential therapeutic strategy to address olaparib resistance in HGSOC and TNBC patients.

PARP enzymes regulate AR via MARylation and PARylation, with inhibitors such as Olaparib, which disrupts AR-PARP crosstalk...We also discuss how this complex regulatory network may contribute to the development of advanced prostate cancer therapies in the future. This could improve PARP inhibitor and AR signalling inhibitor combinations and allow more patients to benefit from them.

P2, N=116, Recruiting, Yonsei University | Not yet recruiting --> Recruiting

P1/2, N=40, Active, not recruiting, Hospices Civils De Lyon | Recruiting --> Active, not recruiting

Our study identifies PrKD1 as a novel modulator of sensitivity to olaparib. Co-targeting PrKD1 using small molecular inhibitors may enhance olaparib efficacy at lower doses and improve PARPi tolerability and therapeutic index. The demonstration of PARP1 at the membrane is novel, introducing the possibility of targeting membranous PARP1 for theranostic applications.

GGT prevalence has increased at RPCCC and informed treatment decisions. Universal point-of-care testing is being implemented with the goal of completing testing for all patients with PDAC seen at RPCCC.

P1/2, N=87, Active, not recruiting, Idience Co., Ltd. | Recruiting --> Active, not recruiting | Trial completion date: Jun 2026 --> Mar 2027 | Trial primary completion date: Sep 2025 --> Jul 2026

P1, N=220, Active, not recruiting, MOMA Therapeutics | Recruiting --> Active, not recruiting

In addition, there are significant differences in sensitivity to most drugs between high-risk and low-risk cohorts, with WIKI4 and Lapatinib negatively correlated with risk scores, while Doramapimod and Niraparib positively correlated with risk scores. The drug sensitivity results also provide drug guidance for the clinical application of this feature, all of which provide important clinical utility for the prognosis of LUAD. At the same time, the intercellular communication network was plotted based on the GRPS score, providing insights into the pathogenesis of LUAD and offering new ideas for developing targeted therapies and precision medicine methods.

Subsequently, we explore how olaparib treatment itself can alter the expression profile of ncRNAs, creating a dynamic feedback loop that may influence therapeutic outcome. By consolidating these findings across various cancers, including ovarian, breast, prostate, and hepatocellular carcinoma, this review highlights the potential of ncRNAs as both predictive biomarkers and therapeutic targets to overcome PARPi resistance and enhance patient outcomes.

In this real-world retrospective cohort, BRCA mutation status was associated with increased risk of clinically significant olaparib-related toxicity. These findings suggest that BRCA mutation status may help identify patients at higher risk of adverse events and support closer toxicity monitoring and individualized dose management during maintenance therapy.