Outcomes of Patients with Advanced Urothelial Carcinoma after Anti–programmed Death-(ligand) 1 Therapy by Fibroblast Growth Factor Receptor Gene Alteration Status: An Observational Study

Kalebasty, Arash Rezazadeh; Benjamin, D. Paul; Loriot, Yohann; Papantoniou, Dimitrios; Siefker‐Radtke, Arlene O.; Necchi, Andrea; Naini, Vahid; Carcione, Jenna Cody; Santiago-Walker, Ademi; Triantos, Spyros; Burgess, Earle F

doi:10.1016/j.euros.2022.11.001

Cited by 2 publications

(3 citation statements)

References 28 publications

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“…Even if there is an assumable connection between these results, there is no clear evidence that FGFR3 alteration would enhance a resistance mechanism against immune checkpoint inhibitors. Some previous studies verified mutated FGFR3 with increased FGFR3 gene expression and an association with decreased T-cell infiltration, but in this publication there was no significant difference in response rate or OS with immunecheckpoint inhibitors in FGFR3 separated groups, possibly due to the lower stromal-mediated immune suppression (17). The controversial manifestation of FGFR3 and PD-L1 in various stages of the examined cystectomic samples in our study suggest a deeper stratification in molecular and immunological status in urothelial carcinomas.…”

Section: Figurecontrasting

confidence: 58%

“…Sweis et al categorised bladder cancer into two subgroups using immune gene profiling; T-cell-inflamed tumors and non-T-cell-inflamed tumors. In the non-T-cell-inflamed subgroup, which is mostly associated with luminal-papillary subtype (or cluster I subtype), they identified some exclusively typical somatic mutation, where FGFR3 was the most common molecular alteration (16,17). Lower response rates and shortened OS following anti-PD-L1 therapy was observed in patients with FGFR alterations (18).…”

Section: Introductionmentioning

confidence: 99%

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Correlation between fibroblast growth factor receptor mutation, programmed death ligand-1 expression and survival in urinary bladder cancer based on real-world data

Révész¹,

Posfai²,

Pajor³

et al. 2023

Pathol. Oncol. Res.

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Background: Programmed cell death (PD)-1/PD-ligand 1 (PD-L1) inhibitors have made a breakthrough in the therapy of advanced urothelial bladder cancer (UBC). The impact of Fibroblast Growth Factor Receptor 3 (FGFR3) mutation on the effectiveness of PD-L1 treatment remains still unclear. Objective: Our study aimed to investigate the frequency of FGFR mutations at different tumor stages, and their relation to PD-L1 status and survival.Methods: 310 patients with urothelial bladder cancer and subsequent radical cystectomy were included in a retrospective study over a 10-year study period at the University of Szeged, Hungary. FGFR3 mutations from the most infiltrative areas of the tumor were analyzed by targeted next-generation sequencing and PD-L1 (28-8 DAKO) tests (tumor positive score -TPS and combined positives score–CPS). In T0 cases FGFR3 mutations were analyzed from the earlier resection samples. Survival and oncological treatment data were collected from the National Health Insurance Fund (NHIF). Neoadjuvant, adjuvant and palliative conventional chemotherapies were allowed; immunotherapies were not. The relationship between the covariates was tested using chi-square tests, and survival analysis was performed using the Kaplan-Meier model and Cox proportional hazards regression.Results: PD-L1 and FGFR could be tested successfully in 215 of the 310 UBC samples [pT0cyst 19 (8.8%); St.0-I 43 (20%); St.II 41 (19%); St.III-IV 112 (52%)]. Significant pairwise dependency was found between tumor stage, FGFR3 mutation status and PD-L1 expression (p < 0.01). Samples with FGFR mutation were more common in less advanced stages and were also less likely to demonstrate PD-L1 expression. The effect of all investigated factors on survival was found to correlate with tumor stage.Conclusion: FGFR alteration frequency varied between the different stages of cancer. Higher positivity rates were observed at early stages, but lower levels of PD-L1 expression were detected in patients with FGFR mutations across at all stages of the disease.

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Section: Figurecontrasting

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Correlation between fibroblast growth factor receptor mutation, programmed death ligand-1 expression and survival in urinary bladder cancer based on real-world data

Révész¹,

Posfai²,

Pajor³

et al. 2023

Pathol. Oncol. Res.

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“…Therapies against other cytokines and signaling pathways in CAFs are explored in different cancers. [100][101][102][103][104][105][106][107] In gratinib [104,105] (BGJ398) is a broblast growth factor receptor 1-3 inhibitor that has shown promising results in advanced and metastatic cholangiocarcinoma with FGFR2 gene fusions or rearrangements. BL-8040 [106] is a CXCR4 antagonist and, when combined with PD-1 blockade, may expand the bene t of chemotherapy in PDAC.…”

Section: Recombinant Fusion Proteinmentioning

confidence: 99%

Recent advances in cancer-associated fibroblast: Biomarkers, signaling pathways, and therapeutic opportunities

Zhou,

Zheng

2024

Chinese Medical Journal

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Anti-cancer therapies usually focus on tumor cells, but non-tumor stromal components in the tumor microenvironment also play vital roles in tumor initiation and progression, which may be the prognostic factors and potential therapeutic targets. Cancer-associated fibroblasts (CAFs) are the essential component in the tumor environment, exhibiting high heterogeneity in their cell origin and phenotype with diverse functions that influence tumor angiogenesis, immune systems, and metabolism. Single-cell RNA sequencing and genetically engineered mouse models have increased our understanding of CAF diversity, and many subtypes have been defined. However, the precise functions of these subtypes need to be studied and validated. Studies of signaling pathways and epigenetic changes in CAFs facilitate understanding of the phenotypes of CAFs and the crosstalk between tumor cells and CAFs to provide potential therapeutic targets. Some clinical trials, including phase III trials targeting CAFs, have been performed recently. However, few of these trials have generated promising results, which indicates that the complexity of CAFs in the tumor microenvironment remains largely unknown, and in-depth investigations of CAFs should be performed. This review summarizes the research on CAFs, focusing on the heterogeneity of their phenotypes and functions, specific signaling pathways, and the therapeutic strategies involving CAFs. Additionally, we briefly discuss the current technologies commonly used in CAF studies and describe the challenges and future perspectives of CAF research.

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Outcomes of Patients with Advanced Urothelial Carcinoma after Anti–programmed Death-(ligand) 1 Therapy by Fibroblast Growth Factor Receptor Gene Alteration Status: An Observational Study

Cited by 2 publications

References 28 publications

Correlation between fibroblast growth factor receptor mutation, programmed death ligand-1 expression and survival in urinary bladder cancer based on real-world data

Correlation between fibroblast growth factor receptor mutation, programmed death ligand-1 expression and survival in urinary bladder cancer based on real-world data

Recent advances in cancer-associated fibroblast: Biomarkers, signaling pathways, and therapeutic opportunities

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