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Review
. 2024 Jul 20;15(1):295.
doi: 10.1007/s12672-024-01173-z.

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

Dereje E Bogale  1
Affiliations
Review

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

Dereje E Bogale. Discov Oncol. .

Abstract

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.

Keywords: Fibroblast growth factor receptor 3; Urothelial bladder cancer; c-MYC.

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Conflict of interest statement

The author declares no competing interests.

Figures

Fig. 1
Fig. 1
Signaling pathways activated by the FGFRs
Fig. 2
Fig. 2
The structure of c-MYC protein. Location of MYC or M boxes (MB) I and II within the transactivation domain (TAD), and MBIII and IV in the central region of the protein. bHLHLZ basic helix-loop-helix leucine zipper
Fig. 3
Fig. 3
An illustration of c-MYC as a key downstream effector of activated FGFR3 mediating tumorigenicity in urothelial bladder cancer. The direct positive regulation of c-MYC on FGFR3 expression is also shown (dashed arrow)
See this image and copyright information in PMC

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