HRD

The five HRD assays varied significantly in HRD detection rates in high-grade serous OC. The results support the applicability of genomic instability analyses to assess HRD, while also highlighting the need to improve harmonization across different assays when HRD is used for therapeutic decision making.

Mechanistically, targeting ATR signaling at multiple levels induced a replication defect, mitotic abnormalities and apoptotic cell death. Taken together, our results demonstrate the therapeutic benefit of targeting DDR mechanisms in sarcoma with HRDness traits and their potential clinical utility for treating a broader spectrum of tumor types.

We also incorporated immune architecture using Structural Similarity Index Measure (SSIM) maps that revealed co-localization of immune infiltration and miRNA topics. This integrative approach highlights how miRNA-based spatial analysis can predict PARP inhibitor resistance and provide a promising biomarker to inform therapeutic strategies for BRCA1/2- related breast cancers.

Clinical implications are direct: SGTs in BRCA1 carriers should not be assumed eligible for PARP inhibitor therapy without HRD confirmation, and enhanced surveillance appears unwarranted. This case underscores that co-occurrence does not establish causation and highlights the critical importance of functional validation before expanding hereditary cancer spectra.

Our HRD-based prediction model offers a reliable tool for CHOL prognosis, suggesting new potential for six candidate genes as prognostic biomarkers. It highlights potential therapeutic targets and drug sensitivities, providing new insights into personalized treatment strategies for CHOL management.

P1/2, N=210, Recruiting, Shanghai SciBrunch Therapeutics Co., Ltd. | Not yet recruiting --> Recruiting

Advances in molecular understanding and diagnostics are beginning to inform the development of targeted therapies. Future work may benefit from integrating cancer neuroscience with computational modelling, standardise diagnostic platforms, and test the survival impact of receptor reassessment in prospective trials.

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.

We propose that future trials involving women with premenopausal ER-positive disease must prioritize biology over age in defining eligibility, incorporate OFS as a SOC in the control arm and expand biomarker-driven approaches to refine both treatment escalation and de-escalation. A genomically and immunologically informed strategy is essential to improve the outcomes in this under-represented population.

Alterations in the homologous recombination (HR) DNA repair pathway are reported in 3.0-19.5% of PDAC patients. These types of alterations can sensitize tumors to platinum-based chemotherapy in PDAC as well as other cancers including ovarian, colorectal, and prostate cancers. Retrospective and prospective studies in locally advanced/metastatic PDAC demonstrate higher response rates and longer survival outcomes among HR-deficient (HRD) patients receiving platinum-based chemotherapy. A growing body of evidence in the neoadjuvant setting suggests a potential benefit for HRD-PDAC patients in terms of enhanced tumor downstaging, higher resectability, and improved survival outcomes compared with HR-proficient patients. However, prospective ad hoc studies are still warranted to confirm these findings Homologous recombination deficiency represents a promising biomarker to guide patient selection for neoadjuvant platinum-based chemotherapy in PDAC. Incorporation of HR deficiency-testing into neoadjuvant treatment schemes will enable a more personalized therapeutic approach, supporting the implementation of precision oncology for early-stage PDAC patients.

For these advanced diseases, the two main questions for surgical strategy are the feasibility of complete resection (without residual disease, CC-0), assessed during surgical exploration of pelvis and abdomen, and the optimal timing of this surgery (upfront or after neoadjuvant chemotherapy). In recurrent diseases, surgery remains a main piece of treatment in case of late relapse and medical treatment depends on drugs used in the first line; in early platinum resistant relapse, a new therapeutic option is available with mirvétuximab soravtansine.