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  • Hosaka, KKarolinska Institutet (author)

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

  • Article/chapterEnglish2020

Publisher, publication year, extent ...

  • 2020-07-24
  • Springer Science and Business Media LLC,2020

Numbers

  • LIBRIS-ID:oai:prod.swepub.kib.ki.se:144322375
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:144322375URI
  • https://doi.org/10.1038/s41467-020-17525-6DOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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.

Added entries (persons, corporate bodies, meetings, titles ...)

  • Yang, YL (author)
  • Seki, TKarolinska Institutet (author)
  • Du, QQ (author)
  • Jing, XKarolinska Institutet (author)
  • He, XK (author)
  • Wu, JY (author)
  • Zhang, Y (author)
  • Morikawa, H (author)
  • Nakamura, M (author)
  • Scherzer, MKarolinska Institutet (author)
  • Sun, XT (author)
  • Xu, YF (author)
  • Cheng, T (author)
  • Li, XR (author)
  • Liu, XL (author)
  • Li, Q (author)
  • Liu, YZ (author)
  • Hong, A (author)
  • Chen, YG (author)
  • Cao, YHKarolinska Institutet (author)
  • Karolinska Institutet (creator_code:org_t)

Related titles

  • In:Nature communications: Springer Science and Business Media LLC11:1, s. 3704-2041-1723

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