Evi/Gpr177 as New Target for Treating and Diagnosing Brain Tumors (P-975)
DKFZ Deutsches Krebsforschungszentrum
The Wnt secretion protein Evi/Grp177
- is upregulated in astrocytic astrocytoma and its high expression correlates with poorprognosis
- supports tumor cell proliferation, invasion and tumor initiation and prevents apoptosis
- constitutes a validated target for glioma treatment and glioma diagnostics.
Malignant astrocytomas constitute most primary brain tumors with poor prognosis for glioma patients and low longterm survival rates. Glioblastoma, the most aggressive form, are characterized by invasive behavior and a high degree of apoptosis resistance leading to limited treatment options. Despite highly aggressive multimodal therapy, including surgical resection followed by combined radio- and chemotherapy, the median survival of glioblastoma patients has remained as low as 12-14 months throughout the past decade.
Lowering the rate of recurrence after tumor removal would greatly improve the poor prognosis for glioma patients.
DKFZ inventors now identified the Wnt secretion protein Evi/Gpr177, which is strikingly upregulated during glioma tumorigenesis in a WHO stage-independent way and which correlated with poor prognosis (p = 0.013). SiRNA-and lentiviral shRNA-based silencing of Evi/Gpr177 significantly inhibited glioma cell proliferation and migration. Additionally an inhibitory antibody against Evi/Gpr177 was invented that significantly reduced Wnt target gene response.
Functional analyses in glioma and glioblastom-derived cancer stem-like cells identified the target molecule as an essential regulator of glioma tumorigenesis. In the following animal studies will be performed, confirming the capability of Evi/Gpr177 as new target forglioma treatment.
Advantages and Commercial Opportunity
Evi/Gpr177 is a core Wnt signalling component and a specific regulator of pan-Wnt protein secretion, affecting both canonical and non-canonical signalling. This fact assigns as vulnerable target for glioma treatment.
Additionally its localization in the membrane facilitates the accessibility to antibodies and compounds. Apart from the role as target, Evi/Gpr177 also can be used as diagnostic marker.
The invention was jointly conceived by Iris Augustin and Michael Boutros of German Cancer Research Center Heidelberg (DKFZ).
A priority patent application was filed April 16, 2011 at the EPA.
“The Wnt secretion protein Evi/Gpr177 promotes glioma tumourigenesis.” in EMBO MolMed. 2012 Jan; 4(1): 38-51. doi:10.1002/emmm.201100186. Epub 2011 Dec7; by Augustin et al.; see:http://www.ncbi.nlm.nih.gov/pubmed/22147553