HRD

P2/3, N=120, Recruiting, N.N. Alexandrov National Cancer Centre

Cost-effectiveness analyses further support the integration of HRD testing at diagnosis, highlighting its role in guiding optimal use of PARP inhibitors and improving healthcare resource allocation. This review summarizes the biological rationale, diagnostic methods, therapeutic implications, and economic considerations of HRD in EOC, with a focus on first-line maintenance strategies and future directions in precision oncology.

This study underscores the presence of sex-specific therapeutic vulnerabilities in GCTs, which warrant further exploration in larger cohorts.

Collectively, VEGF-, PARP-, and FRα-targeted therapies have enabled more rational treatment sequencing, informed combination strategies, and personalized clinical decision-making in ovarian cancer. Ongoing efforts to define optimal sequencing, overcome acquired resistance, and refine predictive biomarkers are expected to further enhance the durability and breadth of benefit from targeted therapies and advance precision oncology in gynecologic malignancies.

Other molecular alterations, such as BRAF (approximately 3%) or MMR deficiency (2-4%), have also been reported. Thus, the identification of pancreatic acinar cell carcinoma should trigger theranostic molecular analyses for treatment personalization.

This study investigated cyclin-dependent kinase 12 (CDK12), a transcriptional regulator of HR genes, and evaluated the efficacy of a novel CDK12 inhibitor, CTX-439, combined with a PARP inhibitor, olaparib, in patient-derived xenograft (PDX) models of USC. Furthermore, CDK12 inhibition enhanced tumor sensitivity to the PARP inhibitor, olaparib in USC PDX models. This study indicates that CDK12 is a potential therapeutic target for enhancing the antitumor effects of PARP inhibitors in patients with USC.

P1/2, N=42, Recruiting, Tubulis GmbH | Not yet recruiting --> Recruiting

This case suggests that the combination of denosumab with PARP inhibitors and chemoradiotherapy may provide a potential therapeutic strategy for TNBC patients with bone metastasis. Further studies are warranted to validate the efficacy and safety of this combined treatment approach.

This case highlights that the co-occurrence of BRAF V600E and biallelic BRCA2 mutations may confer a unique clinical phenotype with suboptimal or transient responses to both BRCA-directed therapies (platinum, olaparib) and BRAF/MEK inhibition. It underscores the complexity of precision oncology in PDAC, where genotype does not always predict therapeutic response, potentially due to factors like tumor heterogeneity, stromal barriers, or undiscovered resistance mechanisms. Future large-scale studies are needed to define prognostic implications and explore potential combination strategies (e.g., BRAF/MEK + PARP inhibitors) for this rare molecular cohort.

Analysis across multiple tumour whole-genome sequencing datasets has shown that HR status prediction algorithms can separate profiles for BRCA1 and BRCA2 pathogenic variants and provide further evidence at increased weight to aid in the classification of germline BRCA1 and BRCA2 variants. Tumour sequencing offers a promising strategy for reducing the uncertainty in germline variant interpretation.

Besides, the best survival occurring in adsOC patients with BRCAm, HRD patients treated with PARPi MT also experienced significantly prolonged PFS and OS. However, prior frontline PARPi MT was associated with poorer OS if the recurrence occurred. Treatment for recurrence status with PARPi MT did not show survival benefits.

Overall survival (OS) favoured HRD, with 5-year OS of 89.2% vs 82.8% in HRP (p = 0.009), with stronger evidence in triple-negative TILs-low disease (p = 0.005). These findings support RAD51-based HRD assessment as a predictive and prognostic biomarker that may guide treatment decisions in early-stage BC.