A bit old...
Xerion's Xstream® Technology Identifies a Novel Target for Cancer Therapy
Press Release Munich / Germany, June 1, 2004
Xerion Pharmaceuticals AG, a privately held company, today announced that Xerion scientists together with their collaborators at Tufts University School of Medicine and the National Cancer Institute have discovered an extracellular form of heat shock protein (hsp) 90 and its role in cancer invasion. The results of the study appear in the June issue of Nature Cell Biology (Volume 6, 2004).
Invasion is a key step in tumor progression that eventually leads to metastases when a disseminated tumor cell penetrates through the extracellular matrix and establishes a secondary tumor site elsewhere. To date there are no effective and safe treatments against metastases due to the lack of reliable validated drug targets. Hsp90 recently has gained significant attention as an important target for cancer therapeutics and hsp90 inhibitors are currently in Phase I and II clinical trials. Since hsp90 is also a key protein for normal cell function, there is some concern about treatment-related toxicity, especially if hsp90 inhibitors are unable to distinguish normal and cancer cells.
In the published article entitled "Functional Proteomic Screens Reveal an Essential Extracellular Role for Hsp90 in Cancer Cell Invasiveness", the researchers used functional screens on the extracellular membrane proteome of a highly invasive hu-man tumor cell line. The screens integrated the use of Xerion's Xstream technology - integrating antibody phage display, Fluorophore-Assisted Light Inactivation (FALI) and mass spectrometry. The screens identified the extracellular hsp90 associated with tumor cell invasion.
The researchers demonstrated a direct physical and functional interaction between hsp90 and matrix metalloprotease (MMP) 2, a primary player in the tumor invasion process. This opens the possibility for developing antibodies against hsp90 for the treatment of cancer.
"This work highlights the relevance of validating function at the protein level. Genetic approaches would have missed the discovery of the novel mechanism of hsp90 action", said Daniel Jay, Ph.D., Professor at Tufts University and senior author of the paper.
"This study introduces a functional proteomic approach using Xstream technology to identify and validate disease-relevant proteins that nicely complements classical ge-netic screens", added Leodevico Ilag, Ph.D., Chief Technology Officer at Xerion Pharmaceuticals and a co-author of the article. "These studies suggest anti-hsp90 antibodies may offer therapeutic options to patients with refractory cancers." |
