TY - JOUR

T1 - Perspective

T2 - targeting VEGF-A and YKL-40 in glioblastoma–matter matters

AU - Holst, Camilla Bjørnbak

AU - Pedersen, Henriette

AU - Obara, Elisabeth Anne Adanma

AU - Vitting-Seerup, Kristoffer

AU - Jensen, Kamilla Ellermann

AU - Skjøth-Rasmussen, Jane

AU - Lund, Eva Løbner

AU - Poulsen, Hans Skovgaard

AU - Johansen, Julia Sidenius

AU - Hamerlik, Petra

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - Angiogenesis

KW - glioblastoma

KW - mouse models

KW - VEGF

KW - YKL-40

U2 - 10.1080/15384101.2021.1901037

DO - 10.1080/15384101.2021.1901037

M3 - Journal article

C2 - 33779510

AN - SCOPUS:85103259589

VL - 20

SP - 702

EP - 715

JO - Cell Cycle

JF - Cell Cycle

SN - 1538-4101

IS - 7

ER -