FOXA1 (Forkhead Box A1)

In recent clinical trials of metastatic ER+ BC, next-generation SERDs demonstrated clinical activity, and elacestrant received an approval for advanced ESR1-mutant disease. NR tumors instead up-regulate multiple ERα-independent proliferative pathways, such as EGFR/MAPK and Hippo/TEAD, which may represent targetable dependencies in NR disease. Modeling resistance and lineage plasticity in vitro, we find that giredestrant-resistant ER+ BC cell lines exhibit profound shifts in chromatin accessibility, with the transcription factors, FOXA1 and FOXM1, implicated in gene expression of NR-upregulated proliferative pathways.

We describe the first reported case of apocrine-type DCIS arising in breast PA. Awareness of this rare entity is essential to avoid misdiagnosis and to clarify its clinicopathological characteristics.

This is accompanied by an accumulation of immunosuppressive myeloid cells, dysfunctional T cells, and immunosuppressive cytokine signaling. Together, these findings demonstrate a tumor-suppressive role for FOXA1 as an enforcer of luminal identity, such that its loss drives basal/squamous de-differentiation, inflammatory response, and immunosuppression.

Notably, FOXA1 and RAB25 are strongly implicated in breast cancer biology, and FOXA1 has been directly linked to the aryl hydrocarbon receptor (AHR), the main regulator of CYP1A1. These results position CEU-938 as a strong precision-therapy candidate that combines target selectivity, a favorable toxicity profile, and biomarker-enabled patient stratification, with potential clinical benefit in ER+ and HER2+ enriched tumors, as well as a subset of TNBC.

Our study, which makes use of the largest Chinese breast cancer sequencing cohort, sought to characterize the age-related genomic profile of breast cancer patients and identify novel therapeutic opportunities for individuals with breast cancer.

BNETs represent a biologically distinct subset of breast cancers with favorable prognostic features and a consistent luminal-like phenotype. However, evidence on optimal treatment remains limited. Further large-scale, prospective studies are needed to define clinical management and validate molecular findings.

In vivo experiment demonstrated that, compared with the control group, the SR-CR synergy group displayed lower tumor weight and tumor volume, elevated spleen index, and fewer M2-TAMs within tumors(all P<0.05). In summary, the SR-CR herbal pair, through mutual reinforcement(Xiang-Xu), concurrently inhibits the AR/FOXA1 signaling axis and arrests M2-TAMs polarization, thereby enhancing anti-PCa efficacy.

These effects apply to both androgen receptor (AR) target genes and other cancer-relevant genes. Our findings thus uncover regulatory features that translate FOXA1 pioneering activity into both activation and repression of transcriptional programs critical for cancer growth.

The methylation status of the MLH1 promoter has limited value in predicting the prognosis of dMMR EEC. Molecular pathways heterogeneity between the methylated and nonmethylated subgroups suggests the necessity of integrate multi-dimensional indicators to optimize stratification strategies, instead of relying on a single epigenetic marker.

Emerging evidence shows profound alterations in this axis in CRPC and in tumors resistant to ARSi therapies. In this review, we highlight the genetic, epigenetic, transcriptional, and posttranscriptional changes within the AR-FOXA1 axis in PCa following ADT and ARSi treatments.

Integrating germline variation and epigenomics through a cistrome-wide association study identified a new BLCA risk locus upstream of SPINK1, and linked 10/19 BLCA risk loci to regulatory elements from a 350,000-sample genome-wide association study (GWAS). Implications: Overall, this integrative computational analysis provides comprehensive insights into the epigenomic underpinnings of BLCA subtypes, nominates candidate master regulators of cellular identity for future experimental validation, and reveals how regulatory elements harboring inherited germline variation may contribute to BLCA risk and biology.

The effects of FOXA1 inhibition on sensitivity to carboplatin and the immune checkpoint inhibitor atezolizumab were also examined. Its overexpression correlates with disease progression, supporting its potential as a biomarker and therapeutic target. Targeting FOXA1 could enhance immunotherapy efficacy and help overcome chemoresistance in ovarian cancer.