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Bladder cancer

Measuring response to treatment

Nature Reviews Urology volume 11, page 663 (2014)Cite this article

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Cellular signalling involving the fibroblast growth factor (FGF) receptor FGFR3 is thought to have a role in bladder cancer pathogenesis, and is a target for the development of therapeutic drugs. Newly published research has confirmed that matrix metalloproteinases (MMPs) are regulated by FGFR3, and that MMPs have potential as pharmacodynamic markers of FGFR3 activity—inhibition of FGFR3 leads to measurable reductions in the elevated urinary levels of MMP-1 and pro-MMP-10 that are observed in patients with bladder cancer.

FGFR3 is a receptor tyrosine kinase that has been implicated as a potential oncogenic driver in the development of a range of human cancers. Activating mutations in FGFR3 are present in 60–70% of low-grade, papillary, non-muscle-invasive bladder tumours, and in 11–16% of muscle-invasive bladder cancer tumours. High levels of wild-type FGFR3 are also found in >40% of muscle-invasive and metastatic bladder cancers. Several small-molecule inhibitors of FGFR3 are under clinical investigation for cancer therapy, so markers are required to assess pharmacodynamic modulation of FGFR3 expression and activity.

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References

  1. Du, X. et al. MMP-1 and pro-MMP-10 as potential urinary pharmacodynamic biomarkers of FGFR3-targeted therapy in patients with bladder cancer. Clin. Cancer Res. 10.1158/1078-0432.CCR-13-3336

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  1. Robert Phillips
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Phillips, R. Measuring response to treatment. Nat Rev Urol 11, 663 (2014). https://doi.org/10.1038/nrurol.2014.302

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