Fibroblast growth factor receptors across urothelial carcinoma landscape

Abstract

Purpose of review Fibroblast growth factor receptor (FGFR) signalling, especially induced by FGFR3, is a crucial factor in the pathogenesis of urothelial carcinoma and was therefore extensively studied over the last decades. In this review, we summarize the most relevant findings of the past two years. Recent findings Recent studies support the concept that FGFR3 mediates a pathway of urothelial carcinogenesis associated with low malignant potential. FGFR3 may represent a highly accurate biomarker for diagnosis and prediction of recurrence, progression or therapy response. The pan FGFR-inhibitor erdafitinib was recently approved for urothelial carcinoma, whereas several other FGFR-targeted drugs are currently undergoing clinical trials. Summary Numerous recent studies focus on the role of FGFR3 in different urothelial carcinoma subtypes and its potential clinical application as noninvasive biomarker, as well as therapeutic target.

New developments in the biology of fibroblast growth factors

“…Activating mutations in FGFR3 cause Achondroplasia, the most common form of dwarfism in humans. Somatic activating mutations or amplification of FGFR3 are pathogenic for several cancers including urothelial, CNS, multiple myeloma, and hepatocellular carcinoma (Ardizzone et al, 2020; Chesi & Bergsagel, 2015; Ertl et al, 2020; Katoh & Nakagama, 2014; Paur et al, 2015). Several inhibitory FGFR3‐specific antibodies have been developed for use in cancers with amplified or activated FGFR3 (Casadei et al, 2019; Kamath et al, 2012; Yin et al, 2016).…”

Pretreatment clinical and hematologic prognostic factors of metastatic urothelial carcinoma treated with pembrolizumab: a systematic review and meta-analysis

“…Despite the advances offered by ICIs, the objective response rate (ORR) of pembrolizumab is around 20% in first-and second-line mUC [3,5]. The development of predictive biomarkers is indispensable for patient selection, specifically with the avenue of multiple novel therapeutic options such as combination therapies and targeted therapies [6][7][8][9]. For intra-tumoral biomarkers, expression of PD-1 ligand PD-L1 has been found to exhibit more or less some predictive value for anti-PD-1-directed therapy in various cancers [10][11][12][13].…”

PD‐L1 expression and FGFR‐mutations among Danish patients diagnosed with metastatic urothelial carcinoma: A retrospective and descriptive study

“…In addition, gene amplifications of FGFR1 and FGFR3 are common in UC with reported rates of 6% and 13%, respectively [9]. Although primarily associated to UC of low malignant potential, FGFR alterations are present in mUC as well, albeit the prevalence is poorly investigated [10,11].…”