BRCA wild-type

Niraparib exhibits antitumor effects and promotes ferroptosis by inhibiting TM4SF1 expression through ALKBH1-mediated 6mA modification in BRCAwt OC. These findings emphasize the potential application of niraparib in BRCAwt OC and reveal the important role of epigenetic regulation in cancer treatment.

In patients demonstrating substantial response to neoadjuvant chemotherapy (CRS 2-3), PARPi maintenance was associated with improved PFS, whereas no benefit was observed for CRS 1. The score may aid counseling regarding PARPi initiation, particularly in BRCA-wildtype patients or where homologous recombination deficiency (HRD) testing access is limited.

Our findings reveal an intrinsic SLFN11-dependent vulnerability in ccRCC that synergizes with alkylating agents to induce an acquired PARP-1 dependency, thereby sensitizing BRCA1/2-WT tumors to PARP inhibition. Therefore, this work uncovers a potential therapeutic strategy for targeting SLFN11-high kidney cancers.

A 40-year-old woman with FIGO stage IVB, BRCA-wildtype HGSOC developed rapid multi-drug resistance following neoadjuvant chemotherapy, optimal cytoreduction, and progression on maintenance olaparib/bevacizumab, gemcitabine, and a USP1 inhibitor. By utilizing topoisomerase I inhibitors, agents like YL205 bypass microtubule-stabilization resistance induced by prior taxane exposure, while "bystander effects" address intratumoral heterogeneity. Longitudinal, biomarker-matched strategies and proactive toxicity management are essential to achieving deep tissue clearance in heavily pretreated HGSOC.

Given the clinical severity, inpatient treatment was promptly initiated with trastuzumab and pertuzumab every three weeks, combined with weekly paclitaxel at a 50% dose reduction. In carefully selected patients, early and sustained HER2-directed therapy can lead to meaningful clinical recovery when options appear limited. Such cases help bridge the evidence gap for this high-risk group and may inform future therapeutic considerations.

In multivariable analysis, Eastern Cooperative Oncology Group (ECOG) performance status was the only independent predictor of poorer survival (hazard ratio 1.97, 95% CI 1.42-2.74, p < 0.01), while gBRCA1/2 status showed no independent association. In this large retrospective cohort of mTNBC patients treated with SG, the presence of gBRCA1/2 was not associated with statistically significant differences in PFS or OS.

Our results demonstrate that deep learning applied to whole-slide images can predict homologous recombination deficiency status with clinically meaningful accuracy and strong generalization across datasets. The model is particularly effective at identifying homologous recombination-proficient patients and may serve as a valuable tool to support or triage molecular testing. Integrating this artificial intelligence tool into routine pathology workflows could improve diagnostic efficiency, reduce costs, and accelerate access to targeted therapies in ovarian cancer.

Platinum-based chemotherapy increased Cyclin-E1 expression. These patients were less likely to benefit from PARP inhibitors (75% are BRCA-wildtype) or mirvetuximab-soravtansine (67% were not FRα-high), highlighting a distinct patient population in need of novel therapies.

Specifically in BRCA1R1699Q mutated cells, and not BRCA1-proficient or -deficient cells, NDE1 loss leads to increased genomic instability. Altogether, our findings highlight the importance to differentiate between patient-derived mutations when assessing novel treatment targets.

Long-term follow-up data from L-MOCA indicates that olaparib maintenance monotherapy shows promising overall survival and tolerable safety profile in Asian PSROC patients, regardless of BRCA or HRD status.

This review advances an evidence-based translational prioritization framework to guide the clinical development of combination strategies for PARP inhibitor-resistant breast cancer. We identify critical gaps in biomarker integration, standardized resistance modeling-particularly in BRCA wild-type disease-and dynamic monitoring of resistance evolution, and propose key directions for future preclinical and early-phase clinical research.

In first-line treatment of advanced ovarian cancer, immunotherapy ± PARPi does not provide PFS benefits in unselected patients. However, efficacy signals in specific subgroups support the need for biomarker-driven strategies and optimized trials.