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Targeting FGFR in bladder cancer : ready for clinical practice?

Stijn De Keukeleire (UGent) , Daan De Maeseneer (UGent) , Celine Jacobs (UGent) and Sylvie Rottey (UGent)
(2020) ACTA CLINICA BELGICA. 75(1). p.49-56
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Organization
Abstract
Objective: To give a brief literature overview of current knowledge regarding FGFR inhibition in bladder cancer. Background: The deeper molecular understanding of bladder urothelial carcinoma (UC) has reshaped the diagnostic and therapeutic landscape of this malignancy. Rapid technological development, including the frequent use of next-generation sequencing (NGS) in clinical practice, has boosted identification and development of potential biomarkers and targeted therapies. Genetic aberrations in the fibroblast growth factor receptor (FGFR)-pathway may drive tumorigenesis and are considered as attractive drug targets in advanced and/or metastatic UC. Several clinical trials have been performed or are ongoing to assess the safety and efficacy of (non-)selective FGFR inhibitors in patients with advanced or metatastic UC. Results: While non-selective FGFR inhibitors have shown limited clinical response with unacceptable toxicity, selective 'pan'-FGFR inhibitors had favourable response rates with manageable toxicity. To predict response, patients were screened for FGFR aberrations using NGS after DNA/RNA extraction of UC tissue specimen or collection of ctDNA or cfDNA. Conclusion: Early clinical trials have shown promising results for targeting FGFR in advanced or metastatic UC, though these findings need to be validated in phase III trials. It seems that FGFR aberrations can be detected in ctDNA and cfDNA as efficiently as in tumour tissue, showing their potential as predictive, non-invasive liquid biomarkers.
Keywords
COMPREHENSIVE MOLECULAR CHARACTERIZATION, UROTHELIAL CARCINOMA, RECURRENCE, EXPRESSION, TRIAL, PEMBROLIZUMAB, COMBINATION, PROGRESSION, MUTATIONS, DOVITINIB, Bladder cancer, Urothelial carcinoma, UC, Targeted therapy, Fibroblast, growth factor receptor, FGFR, biomarkers

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MLA
De Keukeleire, Stijn, et al. “Targeting FGFR in Bladder Cancer : Ready for Clinical Practice?” ACTA CLINICA BELGICA, vol. 75, no. 1, 2020, pp. 49–56.
APA
De Keukeleire, S., De Maeseneer, D., Jacobs, C., & Rottey, S. (2020). Targeting FGFR in bladder cancer : ready for clinical practice? ACTA CLINICA BELGICA, 75(1), 49–56.
Chicago author-date
De Keukeleire, Stijn, Daan De Maeseneer, Celine Jacobs, and Sylvie Rottey. 2020. “Targeting FGFR in Bladder Cancer : Ready for Clinical Practice?” ACTA CLINICA BELGICA 75 (1): 49–56.
Chicago author-date (all authors)
De Keukeleire, Stijn, Daan De Maeseneer, Celine Jacobs, and Sylvie Rottey. 2020. “Targeting FGFR in Bladder Cancer : Ready for Clinical Practice?” ACTA CLINICA BELGICA 75 (1): 49–56.
Vancouver
1.
De Keukeleire S, De Maeseneer D, Jacobs C, Rottey S. Targeting FGFR in bladder cancer : ready for clinical practice? ACTA CLINICA BELGICA. 2020;75(1):49–56.
IEEE
[1]
S. De Keukeleire, D. De Maeseneer, C. Jacobs, and S. Rottey, “Targeting FGFR in bladder cancer : ready for clinical practice?,” ACTA CLINICA BELGICA, vol. 75, no. 1, pp. 49–56, 2020.
@article{8654702,
  abstract     = {Objective: To give a brief literature overview of current knowledge regarding FGFR inhibition in bladder cancer. Background: The deeper molecular understanding of bladder urothelial carcinoma (UC) has reshaped the diagnostic and therapeutic landscape of this malignancy. Rapid technological development, including the frequent use of next-generation sequencing (NGS) in clinical practice, has boosted identification and development of potential biomarkers and targeted therapies. Genetic aberrations in the fibroblast growth factor receptor (FGFR)-pathway may drive tumorigenesis and are considered as attractive drug targets in advanced and/or metastatic UC. Several clinical trials have been performed or are ongoing to assess the safety and efficacy of (non-)selective FGFR inhibitors in patients with advanced or metatastic UC. 
Results: While non-selective FGFR inhibitors have shown limited clinical response with unacceptable toxicity, selective 'pan'-FGFR inhibitors had favourable response rates with manageable toxicity. To predict response, patients were screened for FGFR aberrations using NGS after DNA/RNA extraction of UC tissue specimen or collection of ctDNA or cfDNA. Conclusion: Early clinical trials have shown promising results for targeting FGFR in advanced or metastatic UC, though these findings need to be validated in phase III trials. It seems that FGFR aberrations can be detected in ctDNA and cfDNA as efficiently as in tumour tissue, showing their potential as predictive, non-invasive liquid biomarkers.},
  author       = {De Keukeleire, Stijn and De Maeseneer, Daan and Jacobs, Celine and Rottey, Sylvie},
  issn         = {1784-3286},
  journal      = {ACTA CLINICA BELGICA},
  keywords     = {COMPREHENSIVE MOLECULAR CHARACTERIZATION,UROTHELIAL CARCINOMA,RECURRENCE,EXPRESSION,TRIAL,PEMBROLIZUMAB,COMBINATION,PROGRESSION,MUTATIONS,DOVITINIB,Bladder cancer,Urothelial carcinoma,UC,Targeted therapy,Fibroblast,growth factor receptor,FGFR,biomarkers},
  language     = {eng},
  number       = {1},
  pages        = {49--56},
  title        = {Targeting FGFR in bladder cancer : ready for clinical practice?},
  url          = {http://dx.doi.org/10.1080/17843286.2019.1685738},
  volume       = {75},
  year         = {2020},
}

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