FGFR3 mutation

In the past few years, circulating tumour DNA has emerged as a minimally invasive biomarker, with increasing data supporting its prognostic value and utility for monitoring clinical responses. In this Review, we address these developments and discuss biomarkers that could have clinical utility in patients with aUC.

STAG2 loss alters DREAM target expression, complex composition, and chromatin distribution, and leads to rewiring of chromatin interactions involving DREAM binding motifs in genes critical for cell cycle entry. Our findings provide compelling evidence that STAG2 loss disrupts in 3D genome organization through a novel mechanism involving the DREAM complex, thereby impairing homeostatic quiescence and increasing oncogenic sensitivity.

Treatment for CCUC has varied by case, with some surgeons electing to treat with radical cystectomy while others opting for local resection. Our case helps combat the paucity of literature by further characterizing and contributing to the management of CCUC.

Our findings reveal a distinct molecular signature of UTUC in Southwestern Taiwan, with early- and late-stage tumors showing divergent mutational landscapes. These insights emphasize the importance of molecular stratification in UTUC management and suggest that a broader repertoire of targeted therapies could benefit patients in this high-incidence region.

In a xenograft model driven by an FGFR3S249C-activating mutation, dabogratinib treatment resulted in dose-dependent tumor growth inhibition with tumor regression observed at the highest doses. These preclinical findings are supported by the three case reports from the SURF301 study, which demonstrate early clinical activity in patients with advanced metastatic urothelial carcinoma with an FGFR3 fusion or activating mutation.

The co-occurrence of this sign with synchronous genitourinary malignancies underscores the importance of a multidisciplinary approach to diagnosis and management. Further investigation is warranted to elucidate the precise underlying mechanisms of this rare phenomenon and its potential role in oncologic detection.

The prevalence of gene alterations is consistent with ranges reported in the literature. This analysis provides insights into the distribution of therapeutic or disease-relevant genetic biomarkers in patients with bladder cancer and helps the understanding of patient biomarker profile to support clinical development for patients with bladder cancer.

The detection rate for FGFR1-4 alterations in a real-world, dual-institution cohort of urinary tract carcinomas was reported.

In a xenograft model driven by an FGFR3 S249C activating mutation, dabogratinib treatment resulted in dose-dependent tumor growth inhibition with tumor regression observed at the highest doses. These preclinical findings are supported by the three case reports from the SURF301 study, which demonstrate early clinical activity in advanced mUC patients with an FGFR3 fusion or activating mutation.

The strong specificity and NPV observed across all studies suggest a role of Uromonitor-v2 as a potential tool for NMIBC follow-up, particularly in ruling out recurrence and clarifying doubtful cystoscopy results. However, the unexpectedly low sensitivity reported in this external multicentre validation suggests the need for further investigation before routine clinical implementation.

Erdafitinib (47.37%) was the most frequently used FGFRi drug in clinical studies...In conclusion, UC patients with FGFR3 fusions, especially FGFR3-TACC3 fusions, may benefit more from FGFRi than those with FGFR3 mutations, which highlighted the importance of FGFR3 alteration site test in determining the efficacy of FGFRi-based therapy and enhanced the patient benefit for FGF/FGFR-altered UC. Future studies with larger sample size and individual patient data are needed to confirm these findings and explore the underlying mechanisms of the differential response to FGFRi.

Mutations in FGFR1 and FGFR3 were associated with aggressive disease, suggesting these pathways as potential therapeutic targets. Integrating liquid biopsy with other diagnostic modalities may enhance personalized management and improve prognosis for patients with HCC.