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Glioblastoma multiforme (GBM) is the most malignant primary brain tumor and is characterized by vascular hyperplasia, necrosis, and high cell proliferation. Despite current standard therapies, including surgical resection and chemoradiotherapy, GBM patients survive for only about 15 months after diagnosis. Recently, the U.S. Food and Drug Administration (FDA) has approved an antiangiogenesis medication for recurrent GBM-bevacizumab-which has improved progression-free survival in GBM patients. Although bevacizumab has resulted in significant early clinical benefit, it inescapably predisposes tumor to relapse that can be represented as an infiltrative phenotype. Fundamentally, bevacizumab antagonizes the vascular endothelial growth factor A (VEGF), which is consistently released on both endothelial cells (ECs) and GBM cells. Actually, VEGF inhibition on the ECs leads to the suppression of vascular progression, permeability, and the vasogenic edema. However, the consequence of the VEGF pathway blockage on the GBM cells remains controversial. Nevertheless, a piece of evidence supports the relationship between bevacizumab application and compensatory activation of kinase signaling within GBM cells, leading to a tumor cell invasion known as the main mechanism of bevacizumab-induced tumor resistance. A complete understanding of kinase responses associated with tumor invasion in bevacizumab-resistant GBMs offers new therapeutic opportunities. Thus, this study aimed at presenting a brief overview of preclinical and clinical data of the tumor invasion and resistance induced by bevacizumab administration in GBMs, with a focus on the kinase responses during treatment. The novel therapeutic strategies to overcome this resistance by targeting protein kinases have also been summarized.
This article was published in the following journal.
Name: Cancer biotherapy & radiopharmaceuticals
Src signaling is markedly upregulated in patients with invasive glioblastoma (GBM) after the administration of bevacizumab. The Src family kinase inhibitor dasatinib has been found to effectively bloc...
Glioblastoma multiforme (GBM) is the most malignant primary brain tumor with a median survival of approximately 14 months. Despite aggressive treatment of surgical resection, chemotherapy and radiatio...
The aim of this study was to determine whether apparent diffusion coefficient (ADC) bi-component curve-fitting histogram analysis and volume percentage change (VPC) prior to bevacizumab treatment can ...
In glioblastoma multiforme, the balance between the procoagulant system, anticoagulant system and fibrinolytic system is impaired in favour of hypercoagulability. The aim of this study was to compare ...
High dose bevacizumab delivered via super selective intra-arterial cerebral infusion (SIACI) is one promising clinical trial combination for patients with glioblastoma (GBM). While both continuous int...
This study aims to evaluate the role of Regorafenib in prolonging the overall survival of glioblastoma multiforme patients who progressed after surgery and Stupp regimen with or without be...
This is a randomized, active-controlled, multicenter, open-label, parallel groups, Phase 2 study of DSP-7888 Dosing Emulsion plus Bevacizumab versus Bevacizumab alone in patients with recu...
This randomized phase II trial studies how well giving vaccine therapy with or without bevacizumab works in treating patients with recurrent glioblastoma multiforme that can be removed by ...
This is a single-center (Emory University), open-label, single arm, phase I study to assess safety and toxicity of bortezomib in combination with bevacizumab and escalating doses of temozo...
The optimal treatment of glioblastoma multiforme (GBM) in patients aged ≥70 years with a Karnofsky performance status (KPS)
Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21)
A casein kinase I isoenzyme that plays a role in intracellular signaling pathways including the CELL CYCLE, membrane trafficking, and RNA processing. In DROSOPHILA casein kinase Ialpha has been in regulation of Hedghog and Wingless signaling pathways. Multiple isoforms of casein kinase Ialpha exist and are due ALTERNATIVE SPLICING.
A 150-kDa MAP kinase kinase kinase that may play a role in the induction of APOPTOSIS. It has specificity for MAP KINASE KINASE 3; MAP KINASE KINASE 4; and MAP KINASE KINASE 6.
A NOD-signaling adaptor protein that contains a C-terminal leucine-rich domain which recognizes bacterial PEPTIDOGLYCAN. It signals via an N-terminal caspase recruitment domain that interacts with other CARD SIGNALING ADAPTOR PROTEINS such as RIP SERINE-THEONINE KINASES. It plays a role in the host defense response by signaling the activation of CASPASES and the MAP KINASE SIGNALING SYSTEM.
A Janus kinase subtype that is involved in signaling from a broad variety of CYTOKINE RECEPTORS. The TYK2 kinase is considered the founding member of the janus kinase family and was initially discovered as a signaling partner for the INTERFERON ALPHA-BETA RECEPTOR. The kinase has since been shown to signal from several INTERLEUKIN RECEPTORS.
Vascular relates to blood vessels (Oxford Medical Dictionary) and can be used to describe the supply of blood, a disease affecting the blood vessels or molecules associated with these structures. For example, <!--LGfEGNT2Lhm-->atherosclerosis ...