BRCA wild-type

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.

This first comprehensive analysis of Romanian ovarian cancer patients suggests that integrating sWGS-based genomic instability assessment with BRCA testing can improve HRD detection and reflects the heterogeneity of HR-pathway variants. Preliminary clinical observations were consistent with known HRD-associated treatment responses, although larger studies are needed to confirm these findings.

HIPEC did not significantly improve survival over conventional IP in the overall population, but showed greater benefit in specific subgroups, underscoring the importance of individualized intraperitoneal chemotherapy strategies in OC.

Increased PARPi sensitivity following ALC1 loss can be accurately predicted by endogenous single-stranded DNA levels, identifying a functional biomarker. Together, our studies define the clinical contexts in which the therapeutic utility of PARPi can be expanded by targeting ALC1, whose inhibitors are currently under evaluation in Phase I clinical trials.

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).