Existing antiangiogenic drugs, which target vascular endothelial growth factor (VEGF) or its receptor VEGFR2, disrupt normal vasculature as well as tumour vasculature. Here, Al-Hilal et al. report that the prion-like protein doppel is expressed in the blood vessels of human cancer tissues, but not in normal tissues. In vivo and in vitro studies demonstrated that doppel promotes tumour endothelial cell (TEC) angiogenesis, through interaction with VEGFR2. An orally active glycosaminoglycan, LHbisD4, specifically binds to doppel, causing constitutive internalization of the doppel–VEGFR2 complex, resulting in inhibition of VEGF signalling and suppression of tumour growth in mouse xenograft models.
References
Al-Hilal, T. A. et al. Targeting prion-like protein doppel selectively suppresses tumor angiogenesis. J. Clin. Inves. 126, 1251–1266 (2016)
Rights and permissions
About this article
Cite this article
Crunkhorn, S. Tumour-specific angiogenesis inhibition. Nat Rev Drug Discov 15, 310 (2016). https://doi.org/10.1038/nrd.2016.79
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrd.2016.79