BRCA wild-type

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.

No new safety signals were observed. In the real-world setting, the use of niraparib as a maintenance treatment for newly diagnosed advanced ovarian cancer has been shown to be effective and well tolerated, which is consistent with the results of previous randomized Phase III trials.

P4, N=40, Not yet recruiting, Peking Union Medical College Hospital; Peking Union Medical College Hospital

In this study, we show that FASN contributes to PARPi resistance, and that lansoprazole and 5HLS strongly synergize with olaparib and talazoparib in both BRCA1-mutant and wild-type TNBC cells. 5HLS also facilitates PARPi-induced PARP1 trapping and inhibits BRCA1 expression by inhibiting FASN, contributing to the synergy with PARPi in both BRCA1 wild-type and mutant TNBC cells. Together, these findings suggest that inhibiting FASN with PPIs creates an artificial synthetic lethality, providing a rationale for combining PPIs with PARPi to expand their utility to TNBC patients without germline BRCA1 mutations and to overcome PARPi resistance.

The somatic mutational profile of HGSC remains remarkably stable from diagnosis to relapse. Clinically, this stability suggests that repeat mutational sequencing at relapse is unlikely to yield new actionable findings and may have limited value in guiding treatment decisions. Instead, resistance mechanisms likely arise from epigenetic or non-genetic changes, underscoring the need for future research in these areas and the continued importance of optimal surgical management in selected patients.