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Intrinsic FGFR2 and Ectopic FGFR1 Signaling in the Prostate and Prostate Cancer

Cong Wang1, Ziying Liu1,2, Yuepeng Ke2

  • 1School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.

Frontiers in Genetics
|February 15, 2019
PubMed

Insights

Targeting fibroblast growth factor receptor 1 (FGFR1) signaling offers a novel strategy for treating advanced castrate-resistant prostate cancer (CRPC). Suppressing FGFR1 may inhibit tumor growth and progression in this aggressive disease.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Advanced castrate-resistant prostate cancer (CRPC) presents a significant therapeutic challenge with limited effective treatments.
  • The fibroblast growth factor (FGF) signaling axis, particularly the interplay between FGF receptors (FGFRs), is implicated in prostate cancer (PCa) progression.
  • A shift from the intrinsic FGF7/FGF10-FGFR2 pathway to an ectopic FGFR1 pathway is observed during PCa malignancy.

Purpose of the Study:

  • To elucidate the molecular mechanisms driving CRPC progression.
  • To investigate the role of the ectopic FGFR1 signaling pathway in PCa advancement.
  • To identify novel therapeutic strategies targeting FGFR1 for CRPC treatment.

Main Methods:

  • Analysis of molecular signaling pathways in prostate cancer progression.
  • Investigating the distinct roles of FGFR1 and FGFR2 in epithelial lesions.
  • Evaluating the contribution of FGFR1 signaling to tumor angiogenesis, metabolism, and microenvironment inflammation.

Main Results:

  • Loss of FGFR2 and gain of FGFR1 signaling are associated with prostate cancer progression.
  • FGFR1 and FGFR2, despite structural similarities, mediate distinct cellular signals.
  • Ectopic FGFR1 signaling promotes PCa progression through angiogenesis, metabolic reprogramming, and inflammation.

Conclusions:

  • The ectopic FGFR1 signaling pathway is a key driver of castrate-resistant prostate cancer progression.
  • Suppression of FGFR1 signaling represents a promising novel therapeutic strategy for CRPC.
  • Targeting FGFR1 could offer a new avenue for treating this aggressive form of prostate cancer.
Keywords:
cancer progressioncell signalinggrowth factorprostatereceptor tyrosine kinase

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