FGFR4 as a Biomarker in Squamous Cell Cancers of the Mouth and Oropharynx

Abstract

Head and neck squamous cell carcinoma (HNSCC) is a malignancy associated with severe mortality despite advances in therapy, and it ranks among the top ten most common cancers worldwide, with a large incidence variation according to sex and geographical location. At the moment, no biomarkers are currently available for HNSCC patients; prognosis depends largely on the stage at presentation, with the most important prognostic factor. Fibroblast growth factor receptors (FGFRs) and ligand binding are among the many molecules that are involved in the tumorigenesis process. These receptors, including FGFR4, belong to the receptor tyrosine kinase family leads to cell growth, mitosis, and differentiation. Mutations and amplifications in FGFR4 have been linked to aggressive tumor progression, and metastasis is associated with poor prognosis in HNSCC. In this review, we summarize the FGF/FGFR complex, signalization mechanisms, and the molecular implications of FGFR4 as potential biomarker for HNSCC.

Dissecting the Role of the FGF19-FGFR4 Signaling Pathway in Cancer Development and Progression

“…Meanwhile, accumulating evidence suggests that there could be more variability between FGFR4 and other FGFRs than was initially expected. It has been reported that there are a number of amino-acid substitutions in the tyrosine kinase domains of FGFR4 (Dutra et al, 2015;Katoh, 2016). FGF401 (Weiss et al, 2019;Zhou et al, 2019), BLU9931 , and BLU-554 (Hatlen et al, 2019;Kim et al, 2019) have been reported to be the most highly potent and selective FGFR4 inhibitors.…”

“…FGFR4 has been reported as an oncogenic driver in FGF19positive advanced HCC. A therapeutic strategy against targeting FGF19/FGFR4 is being actively investigated (Dutra et al, 2015;Huynh et al, 2019). Meanwhile, inhibition of FGF19-FGFR4 signaling has been reported to be associated with increased risk of hepatotoxicity and cardiac toxicity (Lin and Desnoyers, 2012).…”