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Updated: Dec 13, 2025

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Therapeutic paradigm of dual targeting VEGF and PDGF for effectively treating FGF-2 off-target tumors

Kayoko Hosaka1, Yunlong Yang1,2, Takahiro Seki1,3

  • 1Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77, Stockholm, Sweden.

Nature Communications
|July 26, 2020
PubMed

Insights

Fibroblast Growth Factor 2 (FGF-2) promotes tumor resistance to anti-angiogenic drugs. Combination therapy targeting VEGF and PDGF overcomes this resistance, offering new treatment strategies for FGF-2 positive cancers.

Area of Science:

  • Oncology
  • Cancer Biology
  • Vascular Biology

Background:

  • Fibroblast Growth Factor 2 (FGF-2) plays a key role in angiogenesis and vascular remodeling.
  • Effective treatments for FGF-2 positive tumors are currently lacking.
  • FGF-2 influences tumor vasculature by recruiting pericytes via a PDGFRβ-dependent pathway.

Purpose of the Study:

  • To investigate the role of FGF-2 in tumor resistance to anti-angiogenic therapies.
  • To explore the efficacy of combination therapy targeting VEGF and PDGF in FGF-2 positive tumors.
  • To elucidate the mechanisms underlying FGF-2-mediated drug resistance.

Main Methods:

  • Utilized FGF-2 positive breast cancer and fibrosarcoma models.
  • Investigated the effect of targeting VEGF and PDGF signaling pathways.
  • Assessed the impact of PDGFRβ inhibition on perivascular coverage and anti-VEGF agent efficacy.

Main Results:

  • FGF-2 positive tumors exhibit intrinsic resistance to drugs targeting VEGF and PDGF alone.
  • Dual targeting of VEGF and PDGF signaling demonstrated superior antitumor effects in preclinical models.
  • Inhibition of PDGFRβ disrupted FGF-2-recruited perivascular coverage, enhancing anti-VEGF therapy efficacy.

Conclusions:

  • FGF-2 acts as a resistance biomarker for anti-VEGF and anti-PDGF monotherapy.
  • FGF-2 is a beneficial marker for combination anti-angiogenic therapy.
  • Combination strategies optimizing different antiangiogenic principles may benefit cancers resistant to monotherapy.

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