Perspective: targeting VEGF-A and YKL-40 in glioblastoma - matter matters

Camilla Bjørnbak Holst*, Henriette Pedersen, Elisabeth Anne Adanma Obara, Kristoffer Vitting-Seerup, Kamilla Ellermann Jensen, Jane Skjøth-Rasmussen, Eva Løbner Lund, Hans Skovgaard Poulsen, Julia Sidenius Johansen, Petra Hamerlik

*Corresponding author af dette arbejde
4 Citationer (Scopus)

Abstract

Glioblastomas (GBM) are heterogeneous highly vascular brain tumors exploiting the unique microenvironment in the brain to resist treatment and anti-tumor responses. Anti-angiogenic agents, immunotherapy, and targeted therapy have been studied extensively in GBM patients over a number of decades with minimal success. Despite maximal efforts, prognosis remains dismal with an overall survival of approximately 15 months.Bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF) antibody, underwent accelerated approval by the U.S. Food and Drug Administration in 2009 for the treatment of recurrent GBM based on promising preclinical and early clinical studies. Unfortunately, subsequent clinical trials did not find overall survival benefit. Pursuing pleiotropic targets and leaning toward multitarget strategies may be a key to more effective therapeutic intervention in GBM, but preclinical evaluation requires careful consideration of model choices. In this study, we discuss bevacizumab resistance, dual targeting of pro-angiogenic modulators VEGF and YKL-40 in the context of brain tumor microenvironment, and how model choice impacts study conclusions and its translational significance.

OriginalsprogEngelsk
TidsskriftCell cycle (Georgetown, Tex.)
Vol/bind20
Udgave nummer7
Sider (fra-til)702-715
Antal sider14
ISSN1538-4101
DOI
StatusUdgivet - 3 apr. 2021

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