Researchers from the School of Medicine of the University of Minho have established WNT6 as a novel oncogene in human glioblastoma, opening opportunities to develop more rational therapies to treat this highly aggressive tumor.
Research at UMinho shows that WNT6 is significantly overexpressed in GBMs, as compared to lower-grade gliomas and non-tumor brain, at the mRNA and protein levels. Functionally, WNT6 increases typical oncogenic activities in GBM cells, including viability, proliferation, stem cell capacity, invasion, migration, and resistance to temozolomide chemotherapy. In an in vivo orthotopic GBM model, WNT6 leads to shorter overall survival of mice, and was associated with increased tumor cell proliferation, stem cell capacity, and anti-apoptotic features of the tumors. Mechanistically, WNT6 contributes to activate typical oncogenic signaling pathways, including RTK and STAT, which intertwined with the WNT pathway may be critical effectors of WNT6-associated aggressiveness in GBM.
The present technology relates to a biomarker of the WNT pathway for use in the treatment of cancer, preferably wherein the biomarker is WNT6.
Another aspect of the present technology relates to a WNT pathway inhibitor for use in a method of treating glioblastoma, preferably proneural glioblastoma, classic glioblastoma, neural glioblastoma, or mesenchymal glioblastoma. The method comprises:
- determining the levels of the WNT6 biomarker in a sample from the subject, and
- comparing the level of the WNT6 biomarker in the sample to a predetermined level of WNT6; wherein if the level of the WNT6 in the sample is higher than the predetermined level of the WNT6, then the subject is administered a therapeutically effective amount of a WNT6inhibitor.
Innovative Aspects and Main advantages
WNT proteins are pleiotropic in their activity, with roles from neurogenesis to stem cell proliferation. Unsurprisingly, WNT aberrant activity has been implicated in various human cancers, including in glioma, and is particularly relevant in the context of cancer stem cells (CSC), which have been pointed as critical for cancer recurrence and resistance to radiochemotherapy. The WNT6 ligand is an activator of the WNT pathway, which only recently was associated with chemoresistance in gastric and bladder cancers, with poor prognosis of esophageal squamous cell carcinoma patients, and with increased risk to colorectal adenoma. Importantly, no studies to date have explored the relevance of WNT6 in human glioma, which is the novelty of the current approach.
Glioblastoma (GBM) is a dramatic brain cancer that affects all ages, from children to adults, remaining universally fatal. Understanding the underlying oncogenic molecular events in GBM is thus a crucial step towards better therapies.
Stage of Development
The final products expected to result from this novel approach, a pharmaceutical composition, a pharmaceutical acceptable excipient and a kit for use in the treatment of glioblastoma are still in proof-of-concept phase.
Intellectual Property Rights
A PCT patent has been filed.
The team is looking for companies willing to discuss research collaborations and/or licensing arrangements for commercial exploitation of the technology.