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

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 ; Cao, Yihai

Nature communications, 2020-07, Vol.11 (1), p.3704-15, Article 3704 [Periódico revisado por pares]

London: Nature Publishing Group

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Título:
Therapeutic paradigm of dual targeting VEGF and PDGF for effectively treating FGF-2 off-target tumors
Autor: 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 ; Cao, Yihai
Assuntos: Ablation ; Angiogenesis ; Antiangiogenic agents ; Antiangiogenics ; Anticancer properties ; Antitumor activity ; Biomarkers ; Blood vessels ; Breast cancer ; Drug delivery ; Fibroblast growth factor ; Fibroblast growth factor 2 ; Fibrosarcoma ; Medicin och hälsovetenskap ; Optimization ; Pericytes ; Platelet-derived growth factor ; Tumors ; Vascular endothelial growth factor ; Vascularization
É parte de: Nature communications, 2020-07, Vol.11 (1), p.3704-15, Article 3704
Descrição: 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.
Editor: London: Nature Publishing Group
Idioma: Inglês

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

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 ; Cao, Yihai

London: Nature Publishing Group

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