Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Noeraparast, M; Krajina, K; Pichler, R; Niedersüss-Beke, D; Shariat, SF; Grünwald, V; Ahyai, S; Pichler, M.
FGFR3 alterations in bladder cancer: Sensitivity and resistance to targeted therapies
CANCER COMMUN. 2024;
Doi: 10.1002/cac2.12602
[OPEN ACCESS]
Web of Science
PubMed
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- Co-Autor*innen der Med Uni Graz
- Ahyai Sascha
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- 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.
- Find related publications in this database (Keywords)
- Bladder Cancer
- Erdafitinib
- FGFR inhibition
- FGFR3 mutations
- Resistance to Erdafitinib
- Tumor Microenvironment