Supplementary Figure 5 from Atu027, a Liposomal Small Interfering RNA Formulation Targeting Protein Kinase N3, Inhibits Cancer Progression

Aleku, Manuela; Schulz, Petra; Keil, Oliver; Santel, Ansgar; Schaeper, Ute; Dieckhoff, Britta; Janke, Oliver; Endruschat, Jens; Durieux, Birgit; Röder, Nadine; Löffler, Kathrin; Lange, Christian; Fechtner, Melanie; Möpert, Kristin; Fisch, Gerald; Dames, Sibylle; Arnold, Wolfgang; Jochims, Karin; Giese, Klaus; Wiedenmann, Bertram; Scholz, Arne; Kaufmann, Jörg

doi:10.1158/0008-5472.22377014.v1

00085472can082428-sup-sfi_g5.pdf (583.17 kB)

Supplementary Figure 5 from Atu027, a Liposomal Small Interfering RNA Formulation Targeting Protein Kinase N3, Inhibits Cancer Progression

journal contribution

posted on 2023-03-30, 18:30 authored by Manuela Aleku, Petra Schulz, Oliver Keil, Ansgar Santel, Ute Schaeper, Britta Dieckhoff, Oliver Janke, Jens Endruschat, Birgit Durieux, Nadine Röder, Kathrin Löffler, Christian Lange, Melanie Fechtner, Kristin Möpert, Gerald Fisch, Sibylle Dames, Wolfgang Arnold, Karin Jochims, Klaus Giese, Bertram Wiedenmann, Arne Scholz, Jörg Kaufmann

Supplementary Figure 5 from Atu027, a Liposomal Small Interfering RNA Formulation Targeting Protein Kinase N3, Inhibits Cancer Progression

History

ARTICLE ABSTRACT

We have previously described a small interfering RNA (siRNA) delivery system (AtuPLEX) for RNA interference (RNAi) in the vasculature of mice. Here we report preclinical data for Atu027, a siRNA-lipoplex directed against protein kinase N3 (PKN3), currently under development for the treatment of advanced solid cancer. In vitro studies revealed that Atu027-mediated inhibition of PKN3 function in primary endothelial cells impaired tube formation on extracellular matrix and cell migration, but is not essential for proliferation. Systemic administration of Atu027 by repeated bolus injections or infusions in mice, rats, and nonhuman primates results in specific, RNAi-mediated silencing of PKN3 expression. We show the efficacy of Atu027 in orthotopic mouse models for prostate and pancreatic cancers with significant inhibition of tumor growth and lymph node metastasis formation. The tumor vasculature of Atu027-treated animals showed a specific reduction in lymph vessel density but no significant changes in microvascular density. [Cancer Res 2008;68(23):9788–98]

Usage metrics

Keywords

Angiogenesis Angiogenesis inhibitors & stimulators Angiogenesis mechanisms Chemotherapy Novel drug delivery systems Drug Targets Preclinical Models Animal models of cancer Xenograft models Progression, Invasion & Metastasis Metastasis

Licence

CC BY

Supplementary Figure 5 from Atu027, a Liposomal Small Interfering RNA Formulation Targeting Protein Kinase N3, Inhibits Cancer Progression

History

ARTICLE ABSTRACT

Usage metrics

Categories

Keywords

Licence

Exports