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The Capital Region of Denmark - a part of Copenhagen University Hospital
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Targeting Human Cancer by a Glycosaminoglycan Binding Malaria Protein

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  1. Molecular Evolution of Early-Onset Prostate Cancer Identifies Molecular Risk Markers and Clinical Trajectories

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  2. Targeting transcriptional addictions in small cell lung cancer with a covalent CDK7 inhibitor

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  3. Integrative Genomic Analyses Reveal an Androgen-Driven Somatic Alteration Landscape in Early-Onset Prostate Cancer

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Plasmodium falciparum engineer infected erythrocytes to present the malarial protein, VAR2CSA, which binds a distinct type chondroitin sulfate (CS) exclusively expressed in the placenta. Here, we show that the same CS modification is present on a high proportion of malignant cells and that it can be specifically targeted by recombinant VAR2CSA (rVAR2). In tumors, placental-like CS chains are linked to a limited repertoire of cancer-associated proteoglycans including CD44 and CSPG4. The rVAR2 protein localizes to tumors in vivo and rVAR2 fused to diphtheria toxin or conjugated to hemiasterlin compounds strongly inhibits in vivo tumor cell growth and metastasis. Our data demonstrate how an evolutionarily refined parasite-derived protein can be exploited to target a common, but complex, malignancy-associated glycosaminoglycan modification.

Original languageEnglish
JournalCancer Cell
Volume28
Issue number4
Pages (from-to)500-14
Number of pages15
ISSN1535-6108
DOIs
Publication statusPublished - 12 Oct 2015

ID: 45788504