BRCA wild-type

In this study, in addition to the induction of apoptosis, the use of PARPis (olaparib and niraparib) as maintenance therapies inhibited cell proliferation by causing cellular senescence to exert potent anticancer effects on Capan-1 (BRCA mutated) and PANC-1 (BRCA wild-type) cells...The inhibition of Bcl-2 through the sequence-dependent combination of navitoclax enhanced the anticancer effects of PARPis by removing senescent cells. Collectively, data from our study demonstrate that the clinical application of PARPis as maintenance therapy could be achieved through the induction of cellular senescence. Furthermore, sequence-dependent combination with senescence-targeting drugs can potentiate pancreatic cancer treatment effects of PARPis regardless of the BRCA status.

In an in vivo TNBC xenograft mouse model, combination treatment with paclitaxel and compound 12 significantly increased BRCA1 stability, reduced the final tumor weight, and decreased the number of Ki-67-positive proliferative cells. Our findings suggest that combination therapy with compound 12 can enhance BRCA1 function and improve chemotherapeutic efficacy. This study highlights CTSS inhibition as a promising therapeutic strategy for TNBC patients with wild-type BRCA1.

In the PSM sensitivity analysis, the median PFS was not reached (95% CI, 19.55-NR) in the niraparib group and was 18.33 months (95% CI, 8.90-25.26) in the bevacizumab group (HR = 0.360, 95% CI, 0.176-0.736; P = .005).ConclusionThis analysis suggests that niraparib may provide a progression-free survival advantage compared with bevacizumab in BRCAwt AOC patients, with both regimens appearing to be generally well tolerated in the real-world setting. These findings offer preliminary reference value for maintenance treatment selection in patients with newly diagnosed BRCAwt AOC.

The findings suggest that BRCA-mutated patients may derive a survival benefit from PDS, whereas surgical timing had a limited impact on BRCA wild-type disease. This result underscores the importance of integrating molecular profiling, particularly BRCA mutation status, with surgical assessment to guide optimal and personalized treatment strategies in the PARPi era.

Post-recurrence, she received off-label maintenance with tamoxifen 20 mg daily for five years and remains disease-free at 70 months...Postoperative chemotherapy with carboplatin-paclitaxel was followed by maintenance niraparib 100 mg twice daily for three years...Complete cytoreductive surgery combined with tailored systemic and maintenance therapies can achieve sustained remission even in advanced-stage BRCA-wild-type patients. Broader molecular profiling and international collaboration are essential to refine management strategies for this rare and aggressive malignancy.

PRO-based surveillance showed satisfactory QOL and stable symptom control in PSROC after long-term period of niraparib maintenance, regardless of BRCA status. This real-world research highlights the significance of long-term usage of niraparib and PROs in PSROC management.

The HALO-Taiwan was the first observational study reporting HRD prevalence of 52.9% among patients with advanced OC in Taiwan. Our findings underscore the need to implement guideline-recommended testing for HRD as a part of the initial diagnostic work-up for all newly-diagnosed advanced high-grade OC patients to optimize treatment strategies.

However, for BRCA-mutated mCRPC, olaparib combined with abiraterone improved PFS (HR = 0.61, 95% CrI = 0.41-0.91) and OS (HR = 0.41, 95% CrI = 0.21-0.80) significantly. For patients with changes in other related DNA repair genes (but not BRCA), olaparib alone was an effective treatment. This information may assist doctors and patients in choosing the most suitable treatment based on the cancer's genetic characteristics.

Moreover, 10n·HCl provoked immunogenic cell death (ICD) and activated the cGAS-STING pathway, thereby stimulating antitumor immunity. These results establish 10n as a promising lead compound for the development of dual PARP/NAMPT inhibitors to treat BRCA wild-type TNBC.

P2, N=30, Not yet recruiting, Peking University Third Hospital

Although HRD is a biomarker used to determine which cancer patients would benefit from PARP inhibitors, a lack of harmonization of tests to determine HRD status makes it challenging to interpret their results. Our study highlights the use of comprehensive whole genome sequencing analysis to better predict HRD and elucidates genomic mechanisms associated with this phenotype.

LTL shortening is associated with BRCA1 mutations, regardless of cancer status. Further validation studies are needed.