We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Therapeutic paradigm of dual targeting VEGF and PDGF for effectively treating FGF-2 off-target tumors.
- Authors
Hosaka, Kayoko; Yang, Yunlong; Seki, Takahiro; Du, Qiqiao; Jing, Xu; He, Xingkang; Wu, Jieyu; Zhang, Yin; Morikawa, Hiromasa; Nakamura, Masaki; Scherzer, Martin; Sun, Xiaoting; Xu, Yuanfu; Cheng, Tao; Li, Xuri; Liu, Xialin; Li, Qi; Liu, Yizhi; Hong, An; Chen, Yuguo
- Abstract
FGF-2 displays multifarious functions in regulation of angiogenesis and vascular remodeling. However, effective drugs for treating FGF-2+ tumors are unavailable. Here we show that FGF-2 modulates tumor vessels by recruiting NG2+ pricytes onto tumor microvessels through a PDGFRβ-dependent mechanism. FGF-2+ tumors are intrinsically resistant to clinically available drugs targeting VEGF and PDGF. Surprisingly, dual targeting the VEGF and PDGF signaling produces a superior antitumor effect in FGF-2+ breast cancer and fibrosarcoma models. Mechanistically, inhibition of PDGFRβ ablates FGF-2-recruited perivascular coverage, exposing anti-VEGF agents to inhibit vascular sprouting. These findings show that the off-target FGF-2 is a resistant biomarker for anti-VEGF and anti-PDGF monotherapy, but a highly beneficial marker for combination therapy. Our data shed light on mechanistic interactions between various angiogenic and remodeling factors in tumor neovascularization. Optimization of antiangiogenic drugs with different principles could produce therapeutic benefits for treating their resistant off-target cancers. Anti-VEGF therapy has many limitations that might be resolved by using combination treatment approaches. Here, the authors demonstrate that the dual-targeting of VEGF and PDGF is required for targeting resistant FGF2+ tumors which depend on the recruitment of pericytes on tumor microvessels.
- Subjects
VASCULAR endothelial growth factor antagonists; VASCULAR endothelial growth factors; PERICYTES; VASCULAR remodeling; TUMORS; TARGETED drug delivery; BIOMARKERS
- Publication
Nature Communications, 2020, Vol 11, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-020-17525-6