BRCA wild-type

This study reveals the mutational spectrum of BRCA1 in patients with acute myeloid leukemia, representing unique missense and novel pathogenic mutations that can be further targeted for designing diagnostic and therapeutic strategies for acute myeloid leukemia.

In this real-world retrospective cohort, BRCA mutation status was associated with increased risk of clinically significant olaparib-related toxicity. These findings suggest that BRCA mutation status may help identify patients at higher risk of adverse events and support closer toxicity monitoring and individualized dose management during maintenance therapy.

CT imaging features were associated with HRD status and prognosis in HGSOC, and the proposed CT-based classification showed fair discriminatory performance.

Moreover, molecular docking and dynamics studies were performed to elucidate the detailed binding mechanism of compound 18 with USP1. Taken together, this study presents a promising class of 1H-pyrazolo[3,4-d]pyrimidine-3-carboxamide derivatives as novel USP1 inhibitors with significant therapeutic potential for the treatment of BRCA1-mutant cancers.

Treatment with paclitaxel monotherapy seems to be less effective in patients with recurrent platinum-resistant BRCAmut ovarian cancer compared with the BRCAwt population. Further clinical studies are needed to confirm these data and investigate potential mechanisms of paclitaxel resistance in BRCAmut carriers.

In this real-world cohort, denosumab use was associated with longer rwPFS in germline BRCA1/2-mutated HR+/HER2- mBC with bone metastases.

Telmisartan depletes tumor PD-L1 but has significant PD-L1-independent clinical translational potential to improve PARPi in BRCA wild-type (WT) tumors and augment tumor immunogenicity.

BRCA2-loss CAPC displays a distinct genomic landscape, marked by robust HRD features, suggesting the potential of higher sensitivity to PARPi. These findings highlight the relevance of HRDsig, and routinely use of CGP in refining patient selection for PARPi and guiding the design of future clinical trials.

Consequently, BRCA2 and Rad51 were then ubiquitinated and degraded to inhibit HR and increase the sensitivity of OC to PARPi. Thus, these findings reveal that the combination of 4C with PARPi leading to "synthetic lethality" is an effective strategy for treating BRCA1/2 wild-type OC.

SLFN11 enhances PARPi sensitivity in EOC by stabilizing PARP1/2 via inhibition of proteotoxic ubiquitination, supporting its role as a biomarker in a BRCA-wild-type EOC cell model where PARPi efficacy is limited by intrinsic resistance. While the application of PARPi in other subtypes of EOC still requires further validation, SLFN11 may improve PARPi response and could be explored as a strategy to address PARPi resistance.

EOC patients with gBRCA-m experienced earlier and more severe CIM, highlighting the need for careful monitoring and tailored management.

P2, N=45, Not yet recruiting, The First Affiliated Hospital of Soochow University