PT  - JOURNAL ARTICLE
AU  - Sofian Al Shboul
AU  - Olimpia E Curran
AU  - Javier A Alfaro
AU  - Fiona Lickiss
AU  - Erisa Nita
AU  - Jacek Kowalski
AU  - Faris Naji
AU  - Rudolf Nenutil
AU  - Kathryn L Ball
AU  - Radovan Krejcir
AU  - Borivoj Vojtesek
AU  - Ted R Hupp
AU  - Paul M Brennan
TI  - Kinomics platform using GBM tissue identifies BTK as being associated with higher patient survival
AID  - 10.26508/lsa.202101054
DP  - 2021 Dec 01
TA  - Life Science Alliance
PG  - e202101054
VI  - 4
IP  - 12
4099  - https://www.life-science-alliance.org/content/4/12/e202101054.short
4100  - https://www.life-science-alliance.org/content/4/12/e202101054.full
SO  - Life Sci. Alliance2021 Dec 01; 4
AB  - 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.