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Kinomics platform using GBM tissue identifies BTK as being associated with higher patient survival

S. Al Shboul, OE. Curran, JA. Alfaro, F. Lickiss, E. Nita, J. Kowalski, F. Naji, R. Nenutil, KL. Ball, R. Krejcir, B. Vojtesek, TR. Hupp, PM. Brennan

. 2021 ; 4 (12) : . [pub] 20211013

Language English Country United States

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc22012094

Grant support
BB/C511599/1 Biotechnology and Biological Sciences Research Council - United Kingdom
BB/J00751X/1 Biotechnology and Biological Sciences Research Council - United Kingdom

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.

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