Urothelial Bladder Cancer: Genomic Alterations in Fibroblast Growth Factor Receptor

Zerdan, Maroun Bou; Bratslavsky, Gennady; Jacob, Joseph M.; Ross, Jeffrey S.; Huang, Richard S.P.; Basnet, Alina

doi:10.1007/s40291-023-00647-0

Cited by 5 publications

(1 citation statement)

References 66 publications

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“…Activation of the receptors by ligand; Fibroblast growth factor (FGF) binding leads to the activation of a series of cascades, which are regulatory to cell growth, differentiation, migration and survival in cells derived from mesoderm and neuroectoderm (Haugsten et al 2010;Qin et al 2019;Suzuki et al 2023). Aberrant expression of FGFRs has been reported to be involved in carcinogenesis and progression of selected human neoplasia including breast cancer (Blanckaert et al 1998;Haugsten et al 2010;Kuroso et al 2010;Helsten et al 2016;Qin et al 2019;Wu et al 2022;Bou Zerdan et al 2023), with FGFR2 suggested as a breast cancer susceptibility gene (Meyer et al 2008;Sun et al 2012). Alterations in molecular structure such as axons 7 and 8 deletion in FGFR3 in breast cancer, and single nucleotide polymorphism (SNP) (Gly/Arg) in FGFR4 in head and neck squamous cell carcinoma causing aberrant expression has also been demonstrated as useful for prognosis prediction (Blanckaert et al 1998;Marsh et al 1999;Jang et al 2001;Zammit et al 2001;Ansell et al 2009).…”

Section: Introductionmentioning

confidence: 99%

Expression and Clinicopathological Relevance of Fibroblast Growth Factor Receptors in Canine Mammary Gland Tumors

2024

Int J Vet Sci

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This study was conducted to determine the expression of fibroblast growth factor receptors (FGFRs) in canine mammary gland tumors (CMT) and to investigate the expression relationship with clinical and histopathological parameters. Fortysix CMT tissues were immunohistochemically probed for the expression of FGFR2, FGFR3 and FGFR4 using rabbit polyclonal antibodies. The expression of each receptor was analyzed (Fisher's exact test) for its relationship with clinical parameters (breed size, age, neuter status, involvement of inguinal mammary gland, number of glands involved) and histopathology (mitotic index, tumor size, tumor grade, PCNA and Vimentin expression). Kaplan-Meier survival and Cox-Regression were performed for survival analysis. The proteins (FGFR2, -3 and -4) were localized to the membrane and cytoplasm. Forty-five tumors (97.8%) expressed both FGFR2 and FGFR3. The FGFR4 was expressed in 42 (91.3%) of the tumors. The expression of FGFR2 was significantly associated with histopathology grade 3 of the tumors (P=0.027). FGFR3 expression was not associated with any clinical or histopathology parameters. FGFR4 expression was associated with large breed dogs (P=0.044), and large tumor size (>3cm) (P=0.045), but none of the proteins expressed predicted post-surgical survival in the dogs. In this study, FGFR2 expression has indicated its usefulness in CMT as an indicator of increased tumor malignancy, while FGFR4 expression has demonstrated the ability to identify high stage tumors. Based on these findings, FGFR2 and 4 can be used as markers for advanced and aggressive CMT.

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Section: Introductionmentioning

confidence: 99%

Expression and Clinicopathological Relevance of Fibroblast Growth Factor Receptors in Canine Mammary Gland Tumors

2024

Int J Vet Sci

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Frequency and Nature of Genomic Alterations in ERBB2-Altered Urothelial Bladder Cancer

Leary,

Enright,

Bakaloudi

et al. 2024

Targ Oncol

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The roles of FGFR3 and c-MYC in urothelial bladder cancer

Bogale

2024

Discov Onc

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Bladder cancer is one of the most frequently occurring cancers worldwide. At diagnosis, 75% of urothelial bladder cancer cases have non-muscle invasive bladder cancer while 25% have muscle invasive or metastatic disease. Aberrantly activated fibroblast growth factor receptor (FGFR)-3 has been implicated in the pathogenesis of bladder cancer. Activating mutations of FGFR3 are observed in around 70% of NMIBC cases and ~ 15% of MIBCs. Activated FGFR3 leads to ligand-independent receptor dimerization and activation of downstream signaling pathways that promote cell proliferation and survival. FGFR3 is an important therapeutic target in bladder cancer, and clinical studies have shown the benefit of FGFR inhibitors in a subset of bladder cancer patients. c-MYC is a well-known major driver of carcinogenesis and is one of the most commonly deregulated oncogenes identified in human cancers. Studies have shown that the antitumor effects of FGFR inhibition in FGFR3 dependent bladder cancer cells and other FGFR dependent cancers may be mediated through c-MYC, a key downstream effector of activated FGFR that is involved tumorigenesis. This review will summarize the current general understanding of FGFR signaling and MYC alterations in cancer, and the role of FGFR3 and MYC dysregulation in the pathogenesis of urothelial bladder cancer with the possible therapeutic implications.

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Urothelial Bladder Cancer: Genomic Alterations in Fibroblast Growth Factor Receptor

Cited by 5 publications

References 66 publications

Expression and Clinicopathological Relevance of Fibroblast Growth Factor Receptors in Canine Mammary Gland Tumors

Expression and Clinicopathological Relevance of Fibroblast Growth Factor Receptors in Canine Mammary Gland Tumors

Frequency and Nature of Genomic Alterations in ERBB2-Altered Urothelial Bladder Cancer

The roles of FGFR3 and c-MYC in urothelial bladder cancer

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