Targetable Pathways in Advanced Bladder Cancer: FGFR Signaling

Xiao, Jin-Fen; Caliri, Andrew W.; Duex, Jason E.; Theodorescu, Dan

doi:10.3390/cancers13194891

Cited by 24 publications

(21 citation statements)

References 94 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, a weak negative correlation between CD155 and FGFR3 was to be expected. As the effectiveness of the combination therapy of PD-1/PD-L1 inhibitors and FGFR inhibitors in metastatic UC has been proven (17,34), the combination therapy of TIGIT inhibitors and FGFR inhibitors may also be useful.…”

Section: Discussionmentioning

confidence: 99%

CD155 immunohistochemical expression in upper tract urothelial carcinoma predicts poor prognosis

et al. 2022

View full text Add to dashboard Cite

A novel immune checkpoint, CD155/T-cell immunoreceptor with Ig and ITIM domains, has been recognized as a new therapeutic target in addition to conventional immune checkpoints, such as anti-programmed cell death protein 1/programmed cell death ligand 1 (PD-L1), for urothelial carcinoma (UC). Fibroblast growth factor receptor (FGFR) is considered another new therapeutic target for UC. As FGFR3-mutant UC may be associated with decreased T-cell infiltration, FGFR3 inhibition may facilitate lymphocyte invasion into the tumor microenvironment. Although a combined effect of immune checkpoint inhibitors and FGFR inhibition is expected, the combined expression profiles of CD155, PD-L1 and FGFR3 have not been evaluated in upper tract UC (UTUC). The present study aimed to investigate the association between CD155 expression and clinicopathological factors in 208 patients with UTUC undergoing radical nephroureterectomy. Furthermore, the expression profiles of CD155, PD-L1 and FGFR3 were compared. Immunohistochemical analysis was performed using tissue microarray specimens and survival analyses were performed using the Kaplan-Meier method and the Cox proportional hazards model. High immunohistochemical expression of CD155 was observed in 177 patients (85.1%) and it was associated with advanced pathological stage and lymphovascular invasion. The survival rate was lower among patients with tumors exhibiting high CD155 expression than among those with tumors with low CD155 expression. In addition, multivariate survival analysis revealed that high CD155 expression was an independent prognostic factor for recurrence (hazard ratio=7.32, 95% CI=1.01-53.35, P=0.049). FGFR3 and immune checkpoint signaling molecules, such as CD155 and PD-L1, had a weak negative correlation. The present results indicated that the expression of CD155 is a useful marker for predicting the recurrence of UTUC. In addition, the immunohistochemical expression profiles of CD155, PD-L1 and FGFR3 may further the understanding of the role of FGFR-targeted therapies in immunotherapy for UTUC.

show abstract

Section: Discussionmentioning

confidence: 99%

CD155 immunohistochemical expression in upper tract urothelial carcinoma predicts poor prognosis

et al. 2022

View full text Add to dashboard Cite

show abstract

“…FGFR signaling is crucial in embryonic development and in adult organism, by the involvement in cell proliferation, cell growth, morphogenesis, angiogenesis, tissue repair and metabolism [ 18 ]. Dysregulation of the FGFR pathway due to FGFR gene amplification, overexpression, mutations and rearrangements with at least 15 fusion partner genes has been reported in many cancers, including hematological malignancies [ 19 , 20 ].…”

Section: Discussionmentioning

confidence: 99%

Small RNA-Seq Reveals Similar miRNA Transcriptome in Children and Young Adults with T-ALL and Indicates miR-143-3p as Novel Candidate Tumor Suppressor in This Leukemia

Dawidowska

Maćkowska-Maślak

Drobna-Śledzińska

et al. 2022

IJMS

View full text Add to dashboard Cite

We aimed to identify miRNAs and pathways specifically deregulated in adolescent and young adult (AYA) T-ALL patients. Small RNA-seq showed no major differences between AYA and pediatric T-ALL, but it revealed downregulation of miR-143-3p in T-ALL patients. Prediction algorithms identified several known and putative oncogenes targeted by this miRNA, including KRAS, FGF1, and FGF9. Pathway analysis indicated signaling pathways related to cell growth and proliferation, including FGFR signaling and PI3K-AKT signaling, with the majority of genes overrepresented in these pathways being predicted targets of hsa-miR-143-3p. By luciferase reporter assays, we validated direct interactions of this miRNA with KRAS, FGF1 and FGF9. In cell proliferation assays, we showed reduction of cell growth upon miR-143-3p overexpression in two T-ALL cell lines. Our study is the first description of the miRNA transcriptome in AYA T-ALL patients and the first report on tumor suppressor potential of miR-143-3p in T-ALL. Downregulation of this miRNA in T-ALL patients might contribute to enhanced growth and viability of leukemic cells. We also discuss the potential role of miR-143-3p in FGFR signaling. Although this requires more extensive validation, it might be an interesting direction, since FGFR inhibition proved promising in preclinical studies in various cancers.

show abstract

“…The most common mutations are hotspot mutations on S249C, R248C and Y373C [23]. In-frame FGFR3-TACC3 fusions are also frequently observed [23,24]. Activation of FGFR occurs via ligand binding to an FGFR monomer, leading to dimerization and subsequent autophosphorylation at intracellular tyrosine residues.…”

Section: Key Pointsmentioning

confidence: 99%

Molecular uropathology and cancer genetics for the urologist: key findings for classification and diagnosis

Compérat

Oszwald

Wasinger

et al. 2022

Current Opinion in Urology

View full text Add to dashboard Cite

Purpose of reviewTo highlight the latest changes in prostate cancer (PCa), urothelial carcinoma, upper tract urothelial carcinoma (UTUC) and renal cell carcinoma (RCC) diagnosis and the impact of genetics in this field.Recent findingsBreast cancer1/2 mutations start to play a major role in PCa treatment with regard to personalized medicine. In urothelial carcinoma an overlap between histological pathological and molecular findings exists, fibroblast growth factor receptor alteration are starting to play a major role, programmed death-ligand 1 although problematic is still important in the treatment setting. UTUC is rare, but genetically different from urothelial carcinoma. In the development of RCC, different genetic pathways such as Von Hippel–Lindau, but also tuberous sclerosis 1/2 and others play a major role in tumor development.SummaryOver the last years, genetics has become increasingly important role in the diagnosis and the treatment of patients with urological malignancies. The upcoming 5th edition (1) of the WHO still considers conventional surgical pathology as the diagnostic gold standard, but molecular pathology is gaining importance not only for diagnosis, but also in personalized treatment, of prostate, kidney cancer and urothelial carcinomas. Therefore, a close collaboration between surgical urology, pathology and oncology departments is mandatory. In this review, we will discuss the latest evolutions in PCa, urothelial carcinoma, upper urinary tract carcinomas and RCC s in the field of genetics in urology.

show abstract

Targetable Pathways in Advanced Bladder Cancer: FGFR Signaling

Cited by 24 publications

References 94 publications

CD155 immunohistochemical expression in upper tract urothelial carcinoma predicts poor prognosis

CD155 immunohistochemical expression in upper tract urothelial carcinoma predicts poor prognosis

Small RNA-Seq Reveals Similar miRNA Transcriptome in Children and Young Adults with T-ALL and Indicates miR-143-3p as Novel Candidate Tumor Suppressor in This Leukemia

Molecular uropathology and cancer genetics for the urologist: key findings for classification and diagnosis

Contact Info

Product

Resources

About