BRCA wild-type

Our findings unveil a novel regulatory mechanism of L1 m6A that governs the DNA damage repair response, providing a potential strategy of targeting METTL3 in combination with PARPi for cancer therapy.

Homologous recombinant deficient tumors are associated with the solid transitional-like morphology, with the BRCA1/2-mutated homologous recombinant deficient cases showing the strongest correlation. Genomic instability score alone may not fully capture the spectrum of homologous recombinant deficient-related phenotypes. The variation in solid transitional-like morphology features among BRCA1- or BRCA2-mutated, BRCA1/2- wild-type with homologous recombinant deficient, and homologous recombinant proficient cases may reflect the diverse biological spectrum of different homologous recombination alterations.

The pattern of mutation-defined POLE/MMR/TP53 group classifications varied in histological subtypes, FIGO stage and clinical outcomes in BRCA wild type EOC. BRCA wild type EOC patients with POLEmut or NSMP had favorable survival than those with MMRmut or TP53mut. The panel could be a potential marker for EOC patients.

This study presents the first detailed characterization of ER signaling alterations in ER-positive/HER2-negative breast cancers with germline BRCA2 PVs, offering insights for the development of targeted therapeutic strategies for this patient population.

Multi-region sequencing of two rapid autopsy cases revealed substantial spatial heterogeneity in mutational burden and structural variants, while core driver events remained conserved. Comprehensive whole-genome profiling of metastatic breast cancer reveals extensive genomic complexity, prevalent non-BRCA mechanisms of homologous recombination deficiency, and broad therapeutic actionability, supporting broader implementation of genome-wide sequencing approaches in advanced disease.

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.