BRCA wild-type

Furthermore, emerging data from biomarker-driven clinical trials highlight the importance of molecular stratification in optimizing treatment outcomes. Integrating PI3K/AKT/mTOR inhibition with PARP blockade represents a promising strategy to expand the therapeutic reach of PARP inhibitors and improve clinical outcomes in ovarian cancer.

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.

We evaluated cell cycle-targeted strategies to overcome HR-proficient chemoresistance using either volasertib (a selective PLK1 inhibitor) or adavosertib (a potent WEE1 inhibitor) in BRCA-WT/HR-proficient and BRCA-mutant/HR-deficient HGSOC models. Functional and xenograft models confirmed selective vulnerability of BRCA-WT tumors to either PLK1 or WEE1 inhibition. Our work highlights a mechanistic framework linking cell cycle checkpoint inhibition to DNA repair pathway selectivity, providing a rationale for targeting mitotic regulators in HR-proficient ovarian cancer-a subgroup with high clinical unmet need.

Notably, senaparib showed superior PFS efficacy compared to veliparib and niraparib. PARPi showed efficacy in improving PFS as maintenance therapy for newly diagnosed advanced OC, although no OS advantage was observed. PROSPERO (CRD420251020275).

Its combined format and accessibility render it well-suited for real-world use in personalized ovarian cancer care. Its additional capacity to reveal more extensive tumor genomic alterations improves clinical decision-making and underscores the importance of integrating HRD scoring with comprehensive molecular profiling in personalized oncology.

HIPEC may provide survival benefit primarily in patients with an unfavorable KELIM score. KELIM may be a clinically useful biomarker to guide patient selection for HIPEC during interval cytoreductive surgery in advanced ovarian cancer.

In BRCAwt AOC patients with LOH-low, PC is a cost-effective first-line treatment compared to PCO in both the USA and China, particularly among PD-L1 CPS ≥ 10 population.

BRCA2 germline-mutated patients obtained significantly greater benefit from olaparib compared to BRCA1-mutated patients. PFS benefit from niraparib (primary or recurrent setting) is comparable to clinical trials. There was no difference in benefit between niraparib and rucaparib in the recurrent setting.

Moreover, the expression levels of protein biomarkers associated with the epithelial-to-mesenchymal transition (EMT), including E-cadherin and SLUG, were remarkably reduced in all tested breast cancer cells. Together, our results show the feasibility of extending the application of PARP inhibitors beyond breast cancer with BRCA1 mutations and optimizing the combinative treatment of PARP inhibitors with antimetastasis ruthenium-based chemotherapy as new therapeutic approaches for TNBC harboring wild-type BRCA1.

BRCA1/2-mutated breast cancer shows an enriched tumor immune microenvironment, and the BRCA-IM model exhibits a good performance in prediction of pCR in BRCA1/2-mutated tumors.

CUP-CC+ subgroup (N = 58) has a significantly longer PFS (HR 0.31, 0.19-0.49) than CUP-CC- (N = 46). Future studies should investigate whether CUP-CC has the potential to personalize poly (ADP-ribose) polymerase inhibitor therapies for patients who are BRCA wild-type, including HRP patients.

Observed treatment efficacy and toxic effects varied across PARP inhibitor regimens; for example, the risk ratio for any recurrence or death in the overall study group ranged from 0.53 (95% CI, 0.40-0.70) for senaparib to 0.83 (95% CI, 0.68-1.00) for olaparib, while the risk ratio for high-grade adverse events ranged from 1.15 (95% CI, 0.64-2.06) for veliparib to 4.73 (95% CI, 2.77-8.07) for niraparib. In this study, no subgroup showed an association between first-line PARP inhibitor maintenance therapy in advanced-stage EOC and improved OS, and findings suggest that the consistency of associated PFS benefits may vary, particularly in homologous recombination proficient and BRCA wild type tumors. Variability in efficacy and toxic effects across subgroups and PARP inhibitor regimens underscores the importance of individualized treatment decisions.