HRD (Homologous Recombination Deficiency)

Specific genomic alterations may help stratify immunotherapy outcomes in recurrent or metastatic cervical cancer. The proposed genomic risk model remains exploratory and requires validation in larger, independent cervical cancer cohorts.

The HGOC HRD-GIS determined by the MyChoice HRD+ CDx assay provides statistically robust evidence for BRCA1 and BRCA2 variant interpretation. This approach may refine variant classification, particularly for variants of uncertain significance, and enhance clinical decision-making in hereditary and tumor-based cancer risk assessment.

These findings indicate that simultaneous restriction of glucose uptake/glycolysis and mitochondrial oxidative phosphorylation, termed "dual metabolic inhibition" cooperatively impairs tumor cell survival. The AMPK/JNK axis appears to be a critical mechanistic link underlying this antitumor effect.

Integration of RNA expression data revealed RAD51D , but not XRCC2 , is exceptionally sensitive to splice-altering variation, with 24% of RAD51D loss-of-function missense variants acting through RNA-mediated mechanisms compared to only 5% in XRCC2 . These SGE datasets provide strong, splice-resolved functional evidence to support variant classification across both genes.

P3, N=110, Active, not recruiting, AstraZeneca | Trial completion date: Apr 2026 --> Feb 2027

Although HBOC-related genetic testing and preventive strategies are widely implemented in Japan, this nationwide survey revealed critical structural and evidence gaps, particularly in institutional capacity and the management of evidence-limited scenarios such as STIC, underscoring the need for system-level improvement.

Moreover, these MDM2-recruiting transcriptional/epigenetic machinery degraders (termed MDM2-TEMADs) consistently impair the homologous recombination repair pathway and confer synthetic lethality with PARP inhibitors. Together, this work elucidates MDM2's central role in pediatric sarcoma pathogenesis and presents dCDK9-010 as a first-in-class, MDM2-recruiting P-TEFb degrader and an exemplary MDM2-TEMAD that enables precise targeting of MDM2-dependent oncogenic transcriptional addiction.

These findings support the investigation of rational combination approaches informed by sensitive detection methods and functional testing to address resistance in ultra-rare cancers. Implications: Integrative multi-omic profiling combined with functional testing in DSRCT reveals patient-specific vulnerabilities and biologically targetable receptor and DNA damage response dependencies, while defining immune states that may inform therapeutic response and rational combination strategies in this rare, fusion-driven cancer.

As these genes have extra-P-body functions, the score serves as a transcriptomic proxy for P-body component enrichment, not a direct measure of P-body activity. Despite this limitation, it offers a clinically useful tool for risk stratification and mechanistic hypotheses.

BRCA-associated pancreatic ductal adenocarcinomas demonstrate recurrent morphologic patterns, including increased glandularity, stromal hyalinization, myxoid stromal change and architectural heterogeneity. These observations provide a framework for future comparative studies investigating morphologic correlates of homologous recombination deficiency in pancreatic cancer. Recognition of these patterns may support consideration of germline or somatic DNA-repair gene testing in appropriate clinical settings.

In this study, testing contributivity was similar or higher that of other studies in the literature, and observed mutations prevalences were similar to that of other screenings of western populations. Harmonising per-centres protocols and enhancing molecular testing contributivity with the screening of circulating DNA samples and expanding its range by including non-BRCA HRR-related genes in all reference centres will enable more patients to be accurately treated by targeted therapies.

P2, N=30, Not yet recruiting, Danatlas Pharmaceuticals Co., Ltd