Role of FGFR3 in bladder cancer: Treatment landscape and future challenges.

Bladder cancer is a heterogeneous malignancy and is responsible for approximately 3.2% of new diagnoses of cancer per year (Sung et al., 2021). Fibroblast Growth Factor Receptors (FGFRs) have recently emerged as a novel therapeutic target in cancer. In particular, FGFR3 genomic alterations are potent oncogenic drivers in bladder cancer and represent predictive biomarkers of response to FGFR inhibitors. Indeed, overall ∼50% of bladder cancers have somatic mutations in the FGFR3 -coding sequence (Cappellen et al., 1999; Turner and Grose, 2010). FGFR3 gene rearrangements are typical alterations in bladder cancer (Nelson et al., 2016; Parker et al., 2014). In this review, we summarize the most relevant evidence on the role of FGFR3 and the state-of-art of anti-FGFR3 treatment in bladder cancer. Furthermore, we interrogated the AACR Project GENIE to investigate clinical and molecular features of FGFR3-altered bladder cancers. We found that FGFR3 rearrangements and missense mutations were associated with a lower fraction of mutated genome, compared to the FGFR3 wild-type tumors, as also observed in other oncogene-addicted cancers. Moreover, we observed that FGFR3 genomic alterations are mutually exclusive with other genomic aberrations of canonical bladder cancer oncogenes, such as TP53 and RB1. Finally, we provide an overview of the treatment landscape of FGFR3-altered bladder cancer, discussing future perspectives for the management of this disease.

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Luigi Formisano reports financial support was provided by Italian Association for Cancer Research. Roberto Bianco reports financial support was provided by Italian Association for Cancer Research. Alberto Servetto reports financial support was provided by Italian Association for Cancer Research. Daniela Esposito reports financial support was provided by Italian Association for Cancer Research. Luigi Formisano reports a relationship with Eli Lilly that includes: speaking and lecture fees. Luigi Formisano reports a relationship with Merck Sharp and Dohme that includes: speaking and lecture fees. Luigi Formisano reports a relationship with Janssen Pharmaceuticals Inc that includes: speaking and lecture fees. Luigi Formisano reports a relationship with Novartis that includes: speaking and lecture fees. Luigi Formisano reports a relationship with Sanofi that includes: board membership and speaking and lecture fees. Luigi Formisano reports a relationship with Bristol Myers Squibb Co that includes: speaking and lecture fees. Luigi Formisano reports a relationship with AstraZeneca that includes: speaking and lecture fees. Alberto Servetto reports a relationship with Eli Lilly that includes: speaking and lecture fees. Alberto Servetto reports a relationship with Merck Sharp and Dohme that includes: speaking and lecture fees. Alberto Servetto reports a relationship with Janssen Pharmaceuticals Inc that includes: speaking and lecture fees. Alberto Servetto reports a relationship with Bristol Myers Squibb Co that includes: travel reimbursement. Alberto Servetto reports a relationship with AstraZeneca that includes: travel reimbursement. Sarah Sacagliarini reports a relationship with Ipsen that includes: speaking and lecture fees. Sarah Scagliarini reports a relationship with Bristol Myers Squibb Co that includes: speaking and lecture fees. Sarah Scagliarini reports a relationship with Merck Sharp and Dohme that includes: speaking and lecture fees. Sarah Scagliarini reports a relationship with Janssen Pharmaceuticals Inc that includes: speaking and lecture fees.