PBRM1 (Polybromo 1)

Although emerging studies are beginning to provide insight, evidence suggests roles for PBRM1, SETD2, and BAP1 in metabolic regulation and in shaping the tumor immune microenvironment in ccRCC. Here, we review recent advances in this field and examine their impact on the management of ccRCC.

This study establishes the first H&E-based Pathomics framework for quantifying CAFs infiltration in RCC, providing a cost-effective and non-invasive tool for preliminary risk stratification. The model's strong correlation with collagen features and its ability to reveal underlying molecular mechanisms highlight its potential for potential value in understanding the stromal microenvironment, though further external validation is required for clinical translation.

These findings require prospective validation to confirm their clinical utility.

This study enhances our understanding of ARID1A regulatory mechanisms, highlighting its phosphorylation as a key driver of breast cancer biology. Future research should validate these kinase-substrate interactions and explore their transcriptional and chromatin-level impacts to develop precision therapies for ARID1A-dysregulated cancers.

This review uniquely integrates mechanistic insights with translational advances, providing a forward-looking synthesis of precision immunotherapy in ccRCC. We also emphasize rational combination strategies, biomarker-guided personalization, and irAE management as key priorities to overcome resistance and improve long-term outcomes.

P2, N=43, Recruiting, University of California, San Diego | Not yet recruiting --> Recruiting

Blocking IL-6 synergistically augmented the antitumor efficacy of anti-PD-1 therapy. Our findings revealed a PBRM1-KDM5C-IL-6 axis that influenced antitumor immunity, indicating a potential immunotherapeutic strategy in PBRM1-deficient ccRCC.

PBRM1 maintains chromatin accessibility for hepatocyte differentiation-related genes. Its loss promotes differentiation toward cholangiocytes during injury or tumorigenesis, driving iCCA development.

Furthermore, we developed a machine learning-based prognostic framework using enhancer hijacking signatures. Collectively, this work establishes a valuable resource for ccRCC research by elucidating how SVs and 3D genome reorganization collectively drive oncogenesis, and translates these findings into a clinically applicable prognostic tool.

Proteome-wide degradation selectivity was further characterized by ranking the degraded targets according to the reduction extent of their protein half-lives. Interestingly, the AuPROTAC degraded a relatively limited number of proteins (95) when compared to ACBI2 (221).

Clinical evidence indicates that immune checkpoint inhibitors and targeted vaccines yield limited efficacy as monotherapies, highlighting the immune-excluded phenotype and the scarcity of PD-L1 protein expression as primary obstacles. Future therapeutic breakthroughs will require rational combination strategies, including CAR-T cell therapies targeting novel antigens (e.g., B7-H3) and adoptive T-cell transfer, designed to dismantle stromal barriers and exploit systemic anti-tumor immunity.

Elevated HRD genomic scores in clear-cell RCC correlate with a worse prognosis and an immunologically exhausted microenvironment. From a therapeutic point of view, PARP inhibitor monotherapy has exhibited initial efficacy in small cohorts with high levels of DDR mutation, yet remains investigational for RCC.