FGFR3 alterations in bladder cancer: Sensitivity and resistance to targeted therapies
Abstract In this review, we revisit the pivotal role of fibroblast growth factor receptor 3 (FGFR3) in bladder cancer (BLCA), underscoring its prevalence in both non‐muscle‐invasive and muscle‐invasive forms of the disease. FGFR3 mutations in up to half of BLCAs play a well‐established role in tumor...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-10-01
|
| Series: | Cancer Communications |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cac2.12602 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850283189405220864 |
|---|---|
| author | Maxim Noeraparast Katarina Krajina Renate Pichler Dora Niedersüß‐Beke Shahrokh F Shariat Viktor Grünwald Sascha Ahyai Martin Pichler |
| author_facet | Maxim Noeraparast Katarina Krajina Renate Pichler Dora Niedersüß‐Beke Shahrokh F Shariat Viktor Grünwald Sascha Ahyai Martin Pichler |
| author_sort | Maxim Noeraparast |
| collection | DOAJ |
| description | Abstract In this review, we revisit the pivotal role of fibroblast growth factor receptor 3 (FGFR3) in bladder cancer (BLCA), underscoring its prevalence in both non‐muscle‐invasive and muscle‐invasive forms of the disease. FGFR3 mutations in up to half of BLCAs play a well‐established role in tumorigenesis, shaping distinct tumor initiation patterns and impacting the tumor microenvironment (TME). Emphasizing the importance of considering epithelial‐mesenchymal transition profile and TME status, we revisit their relevance in predicting responses to immune checkpoint inhibitors in FGFR3‐mutated BLCAs. This writing highlights the initially promising yet transient efficacy of the FGFR inhibitor Erdafitinib on FGFR3‐mutated BLCA, stressing the pressing need to unravel resistance mechanisms and identify co‐targets for future combinatorial studies. A thorough analysis of recent preclinical and clinical evidence reveals resistance mechanisms, including secondary mutations, epigenetic alterations in pathway effectors, phenotypic heterogeneity, and population‐specific variations within FGFR3 mutational status. Lastly, we discuss the potential of combinatorial treatments and concepts like synthetic lethality for discovering more effective targeted therapies against FGFR3‐mutated BLCA. |
| format | Article |
| id | doaj-art-9e3eb5c1f9b94eb79fa47e4b178e90be |
| institution | OA Journals |
| issn | 2523-3548 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Communications |
| spelling | doaj-art-9e3eb5c1f9b94eb79fa47e4b178e90be2025-08-20T01:47:48ZengWileyCancer Communications2523-35482024-10-0144101189120810.1002/cac2.12602FGFR3 alterations in bladder cancer: Sensitivity and resistance to targeted therapiesMaxim Noeraparast0Katarina Krajina1Renate Pichler2Dora Niedersüß‐Beke3Shahrokh F Shariat4Viktor Grünwald5Sascha Ahyai6Martin Pichler7Translational Oncology II. Med Clinics Hematology and Oncology Augsburg GermanyTranslational Oncology II. Med Clinics Hematology and Oncology Augsburg GermanyDepartment of Urology Medical University of Innsbruck Innsbruck AustriaDepartment of Hematology and Oncology Clinics Ottakring Vienna AustriaDepartment of Urology Medical University of Vienna Vienna AustriaInterdisciplinary Genitourinary Oncology Clinic for Urology, Clinic for Medical Oncology University Hospital Essen, Hufelandstraße 55 Essen GermanyDepartment of Urology Medical University of Graz Graz AustriaTranslational Oncology II. Med Clinics Hematology and Oncology Augsburg GermanyAbstract In this review, we revisit the pivotal role of fibroblast growth factor receptor 3 (FGFR3) in bladder cancer (BLCA), underscoring its prevalence in both non‐muscle‐invasive and muscle‐invasive forms of the disease. FGFR3 mutations in up to half of BLCAs play a well‐established role in tumorigenesis, shaping distinct tumor initiation patterns and impacting the tumor microenvironment (TME). Emphasizing the importance of considering epithelial‐mesenchymal transition profile and TME status, we revisit their relevance in predicting responses to immune checkpoint inhibitors in FGFR3‐mutated BLCAs. This writing highlights the initially promising yet transient efficacy of the FGFR inhibitor Erdafitinib on FGFR3‐mutated BLCA, stressing the pressing need to unravel resistance mechanisms and identify co‐targets for future combinatorial studies. A thorough analysis of recent preclinical and clinical evidence reveals resistance mechanisms, including secondary mutations, epigenetic alterations in pathway effectors, phenotypic heterogeneity, and population‐specific variations within FGFR3 mutational status. Lastly, we discuss the potential of combinatorial treatments and concepts like synthetic lethality for discovering more effective targeted therapies against FGFR3‐mutated BLCA.https://doi.org/10.1002/cac2.12602Bladder CancerErdafitinibFGFR inhibitionFGFR3 mutationsResistance to ErdafitinibTumor Microenvironment |
| spellingShingle | Maxim Noeraparast Katarina Krajina Renate Pichler Dora Niedersüß‐Beke Shahrokh F Shariat Viktor Grünwald Sascha Ahyai Martin Pichler FGFR3 alterations in bladder cancer: Sensitivity and resistance to targeted therapies Cancer Communications Bladder Cancer Erdafitinib FGFR inhibition FGFR3 mutations Resistance to Erdafitinib Tumor Microenvironment |
| title | FGFR3 alterations in bladder cancer: Sensitivity and resistance to targeted therapies |
| title_full | FGFR3 alterations in bladder cancer: Sensitivity and resistance to targeted therapies |
| title_fullStr | FGFR3 alterations in bladder cancer: Sensitivity and resistance to targeted therapies |
| title_full_unstemmed | FGFR3 alterations in bladder cancer: Sensitivity and resistance to targeted therapies |
| title_short | FGFR3 alterations in bladder cancer: Sensitivity and resistance to targeted therapies |
| title_sort | fgfr3 alterations in bladder cancer sensitivity and resistance to targeted therapies |
| topic | Bladder Cancer Erdafitinib FGFR inhibition FGFR3 mutations Resistance to Erdafitinib Tumor Microenvironment |
| url | https://doi.org/10.1002/cac2.12602 |
| work_keys_str_mv | AT maximnoeraparast fgfr3alterationsinbladdercancersensitivityandresistancetotargetedtherapies AT katarinakrajina fgfr3alterationsinbladdercancersensitivityandresistancetotargetedtherapies AT renatepichler fgfr3alterationsinbladdercancersensitivityandresistancetotargetedtherapies AT doraniedersußbeke fgfr3alterationsinbladdercancersensitivityandresistancetotargetedtherapies AT shahrokhfshariat fgfr3alterationsinbladdercancersensitivityandresistancetotargetedtherapies AT viktorgrunwald fgfr3alterationsinbladdercancersensitivityandresistancetotargetedtherapies AT saschaahyai fgfr3alterationsinbladdercancersensitivityandresistancetotargetedtherapies AT martinpichler fgfr3alterationsinbladdercancersensitivityandresistancetotargetedtherapies |