BRCA1 (Breast cancer 1, early onset)

In heavily pretreated, advanced solid tumor patients with PV in BRCA1/2, adavosertib treatment resulted in low ORR, and this trial did not meet the primary end point.

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.

Through structure-based virtual screening, our results suggest that Ziprasidone and Apomorphine may disrupt the BARD1-XRCC5 interaction...Our findings unveil a novel LLPS-mediated mechanism by which BARD1 confers TMZ resistance in GBM, positioning it as a prognostic marker and a therapeutic target. Targeting the BARD1-XRCC5 axis presents a promising strategy to overcome chemoresistance.

We found that RNA-binding protein RBM38 is correlated with exon 4 inclusion, and RBM38 knockdown further sensitized BRCA1-mutant cells to MEK1 inhibition. Together, these findings define an RBM38-HORMAD1 signaling as a potential therapeutic vulnerability in BRCA1-mutant breast cancer and suggest that targeting splicing regulation may represent a promising strategy to enhance treatment efficacy.

These TNBC cells were significantly more sensitive to cisplatin than wild-type TNBC cells, consistent with our clinical data. In conclusion, RAD51D-deficient tumors were shown to have a phenotype similar to that of BRCA1-deficient tumors, and further investigation of responses to DNA-damaging agents, particularly platinum-based chemotherapy, is warranted.

Similarly, in endometrial cancer, CRISPR tools have elucidated mechanisms of hormonal resistance and facilitated the development of in vivo models via somatic gene editing. This review highlights recent advances in the application of CRISPR/Cas technology to gynecologic malignancies, discussing its potential as both a therapeutic and research platform while acknowledging current limitations and translational hurdles.

BRCA PV, particularly BRCA1, were strongly associated with pCR in pembrolizumab-treated early TNBC. These findings should be considered hypothesis-generating and warrant confirmation in larger prospective cohorts.

TN likely has a cytostatic effect selectively in TNBC cells, indicating functional suppression of tumorigenic properties. Further studies are required to elucidate the underlying mechanisms, and its potential use in combinatorial therapies.

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.

Identification of men at high PCa risk is feasible using age and ethnicity primary care data, but FH coding is unreliable. Test-first invitations improved engagement. Disparities affecting Black men highlight the need for tailored outreach, and better coding of risk factors will facilitate risk-adapted screening.

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

Upstream regulators of the homologous recombination (HR) repair pathway are promising targets for overcoming temozolomide (TMZ) resistance. Both compounds inhibited H3K27Ac and were detectable in orthotopic tumors by LC-MS/MS and significantly extended survival alone and in combination with TMZ. These findings suggest that the RBBP4/p300-axis is a key regulator of HR-mediated repair of TMZ-induced DSBs, and inhibition by either CCS1477 or NEO2734 may be beneficial as monotherapy, but further studies are needed to determine the benefit of combining these agents with TMZ.