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Fibroblast growth factor receptors as therapeutic targets in clear-cell renal cell carcinoma

Guru Sonpavde1, Christopher D Willey, Sunil Sudarshan

  • 1University of Alabama at Birmingham Comprehensive Cancer Center, Division of Hematology and Oncology , 1720 2nd Avenue South, WTI 5, Birmingham, AL 35294-3300 , USA +1 205 975 3742 ; +1 205 934 9511 ; gsonpavde@uabmc.edu.

Expert Opinion on Investigational Drugs
|January 7, 2014
PubMed
Abstract

Insights

Resistance to VEGF-targeted therapy in metastatic clear-cell renal cell carcinoma (RCC) may be overcome by targeting the fibroblast growth factor (FGF) pathway. FGF receptor inhibitors show clinical activity, suggesting a role in optimizing RCC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Metastatic clear-cell renal cell carcinoma (RCC) is driven by pro-angiogenic signaling, notably the VEGF pathway.
  • Current VEGF-targeted therapies face acquired resistance, leading to tumor regrowth and revascularization.
  • This resistance is linked to activation of compensatory angiogenesis pathways, such as the fibroblast growth factor (FGF) pathway.

Purpose of the Study:

  • To review the role of the FGF pathway in resistance to VEGF-targeted therapy in RCC.
  • To explore the rationale for targeting the FGF pathway in RCC treatment.
  • To evaluate the clinical activity of FGF receptor inhibitors in RCC.

Main Methods:

  • Literature search of PubMed and congress abstracts (ASCO, ESMO).
  • Inclusion of preclinical and clinical data for FGF inhibitors in RCC.
  • Review of data on VEGF-targeted therapy resistance mechanisms.

Main Results:

  • The FGF pathway is a logical target for overcoming resistance to VEGF inhibition in RCC.
  • Clinical trials of FGF receptor inhibitors (regorafenib, dovitinib, nintedanib, lenvatinib, cediranib) demonstrated clinical activity.
  • FGF pathway inhibition shows promise in managing metastatic clear-cell renal cell carcinoma.

Conclusions:

  • Targeting the FGF pathway is a promising strategy for advanced RCC.
  • Further clinical development should focus on patient selection and combination therapies.
  • Optimizing FGF pathway inhibition can improve outcomes for patients with refractory RCC.

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