Artikel ; Online: Perspective: targeting VEGF-A and YKL-40 in glioblastoma - matter matters.
2021 Band 20, Heft 7, Seite(n) 702–715
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 ...
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. |
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Mesh-Begriff(e) | Animals ; Antineoplastic Agents, Immunological/administration & dosage ; Bevacizumab/administration & dosage ; Brain Neoplasms/drug therapy ; Brain Neoplasms/metabolism ; Chitinase-3-Like Protein 1/antagonists & inhibitors ; Chitinase-3-Like Protein 1/metabolism ; Drug Delivery Systems/methods ; Drug Resistance, Neoplasm/drug effects ; Drug Resistance, Neoplasm/physiology ; Glioblastoma/drug therapy ; Glioblastoma/metabolism ; Humans ; Mice ; Mice, Inbred NOD ; Tumor Microenvironment/drug effects ; Tumor Microenvironment/physiology ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Vascular Endothelial Growth Factor A/metabolism ; Xenograft Model Antitumor Assays/methods |
Chemische Substanzen | Antineoplastic Agents, Immunological ; CHI3L1 protein, human ; Chitinase-3-Like Protein 1 ; VEGFA protein, human ; Vascular Endothelial Growth Factor A ; Bevacizumab (2S9ZZM9Q9V) |
Sprache | Englisch |
Erscheinungsdatum | 2021-03-28 |
Erscheinungsland | United States |
Dokumenttyp | Journal Article ; Research Support, Non-U.S. Gov't |
ZDB-ID | 2146183-1 |
ISSN | 1551-4005 ; 1538-4101 ; 1554-8627 |
ISSN (online) | 1551-4005 |
ISSN | 1538-4101 ; 1554-8627 |
DOI | 10.1080/15384101.2021.1901037 |
Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
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