Kinomics platform using GBM tissue identifies BTK as being associated with higher patient survival
Open Access
- 13 October 2021
- journal article
- Published by Life Science Alliance, LLC in Life Science Alliance
- Vol. 4 (12), e202101054
- https://doi.org/10.26508/lsa.202101054
Abstract
Better understanding of GBM signalling networks in-vivo would help develop more physiologically relevant ex vivo models to support therapeutic discovery. A “functional proteomics” screen was undertaken to measure the specific activity of a set of protein kinases in a two-step cell-free biochemical assay to define dominant kinase activities to identify potentially novel drug targets that may have been overlooked in studies interrogating GBM-derived cell lines. A dominant kinase activity derived from the tumour tissue, but not patient-derived GBM stem-like cell lines, was Bruton tyrosine kinase (BTK). We demonstrate that BTK is expressed in more than one cell type within GBM tissue; SOX2-positive cells, CD163-positive cells, CD68-positive cells, and an unidentified cell population which is SOX2-negative CD163-negative and/or CD68-negative. The data provide a strategy to better mimic GBM tissue ex vivo by reconstituting more physiologically heterogeneous cell co-culture models including BTK-positive/negative cancer and immune cells. These data also have implications for the design and/or interpretation of emerging clinical trials using BTK inhibitors because BTK expression within GBM tissue was linked to longer patient survival.Funding Information
- Hashemite University
- European Regional Development Fund (No.CZ.02.1.01/0.0/0.0/16_019/0000868)
- Ministry of Health, Czech Republic MH CZ - DRO (00209805)
- BBSRC (BB/C511599/1 and BB/J00751X/1)
- The Edinburgh Brain Cancer Development Fund, European Regional Development Fund
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