FGFR3 (Fibroblast growth factor receptor 3)

This IHC-based, biologically informed stratification identifies an occult aggressive subset within luminal tumors and complements routine pathology. The internally validated nomogram is exploratory given cohort composition and lack of external validation; multicenter validation is warranted.

This review provides an in-depth exploration of the molecular mechanisms, diagnostic performance (sensitivity and specificity), current clinical applications and limitations of various biomarkers, placing a particular emphasis on comparing the differential expression of the same biomarker across different cancer types. By building on this foundation, this review further outlines future development pathways, including multibiomarker combination strategies, AI-assisted analysis and standardised testing protocols, to offer comprehensive references for the early, noninvasive and precise diagnosis of urological tumours.

The dUM significantly outperformed its qPCR predecessor and cytology in sensitivity for detecting NMIBC recurrence in a real-world setting, without compromising specificity. Its high NPV supports its potential for reducing unnecessary cystoscopies. Furthermore, its combination with cystoscopy drastically increased the PPV, suggesting a role as an adjunctive tool to improve diagnostic confidence and potentially reduce unnecessary transurethral resections of bladder tumour, pending favourable cost-effectiveness.

Genetic or pharmacological targeting of S100A6-FGFR3 signaling effectively suppressed BAP1-deficient UM metastasis in preclinical models, highlighting the therapeutic potential of targeting this signaling pathway. Overall, our findings establish S100A6 as a critical mediator of hepatic metastasis in BAP1-deficient UM through FGFR3-dependent tumor microenvironment activation, revealing its therapeutic potential.

Our results indicate that early-onset bladder cancer is a distinct patient population that has disease driven by specific somatic mutations, some of which represent therapeutic targets. This suggests potential benefits of genomic tumor profiling in guiding personalized treatment.

Notably, it showed minimal activity in non-FGFR2-dependent cells. This work presents a new class of selective FGFR2 inhibitors based on a novel scaffold, offering promising lead compounds for the development of FGFR2-target therapies.

Pralsetinib was added to osimertinib, resulting in a response lasting 4 months...After one month with alectinib only, osimertinib was added due to the progression, resulting in another response of more than two months. Upon progression with quadruple alterations (EGFR 19del, EGFR C797S, MET amplification, and RET fusions), cabozantinib-gefitinib combination was initiated, leading to rapid deterioration...At the same time, comprehensive genomic testing remains essential for therapeutic decision-making, with ctDNA analysis complementing tissue-based approaches. Notably, the FGFR3-TACC3 fusion may represent a novel resistance mechanism contributing to the limited efficacy of EGFR-TKI.

Differences between canonical encoders were modest relative to task-specific variability. GOLDMARK establishes a shared experimental substrate for computational pathology, enabling reproducible benchmarking and direct comparison of methods across datasets and models.

Pan-cancer targeted sequencing provided a comprehensive genomic landscape of UBC, capturing canonical drivers and additional alterations that may be overlooked by bladder-restricted assays. The identification of TP53 and STAG2 as prognostic markers highlights the potential value of broader genomic profiling for biologically informed risk stratification in urothelial bladder cancer.

To rigorously validate this framework and overcome the limitations of public bulk datasets, we combined cross-cohort statistical benchmarking with original RNA-sequencing data generated from a laboratory-derived palbociclib-resistant model (MCF7-PR)...In application, the framework identified sorafenib as a top-ranked candidate for reversing CDK4/6i resistance... This study presents TIHS as a mechanism-agnostic, experimentally validated bridge between resistance-state transcriptomes and clinical decision-making. By coupling computational prioritization with in vitro functional verification, we demonstrate that targeting topology-defined hubs is a viable strategy for overcoming therapy resistance.

The analysis reveals a clear trajectory toward more rigorous scientific inquiry in UTUC investigations, with particular emphasis on developing standardized protocols for tumor localization, surgical approaches, and novel treatment modalities. This evolving paradigm reflects the discipline's dedication to advancing therapeutic precision while minimizing risks, suggesting significant potential for subsequent research to refine clinical decision-making and improve prognostic results.