RT Journal Article
SR Electronic
T1 Kinomics platform using GBM tissue identifies BTK as being associated with higher patient survival
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202101054
DO 10.26508/lsa.202101054
VO 4
IS 12
A1 Sofian Al Shboul
A1 Olimpia E Curran
A1 Javier A Alfaro
A1 Fiona Lickiss
A1 Erisa Nita
A1 Jacek Kowalski
A1 Faris Naji
A1 Rudolf Nenutil
A1 Kathryn L Ball
A1 Radovan Krejcir
A1 Borivoj Vojtesek
A1 Ted R Hupp
A1 Paul M Brennan
YR 2021
UL https://www.life-science-alliance.org/content/4/12/e202101054.abstract
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.