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• W3198986309 abstract "Glioblastoma (GBM) is the most malignant primary brain tumor without effective therapies. Since bevacizumab was FDA approved for targeting vascular endothelial growth factor receptor 2 (VEGFR2) in adult patients with recurrent GBM, targeted therapy against receptor tyrosine kinases (RTKs) has become a new avenue for GBM therapeutics. In addition to VEGFR, the epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), hepatocyte growth factor receptor (HGFR/MET), and fibroblast growth factor receptor (FGFR) are major RTK targets. However, results from clinical Phase II/III trials indicate that most RTK-targeting therapeutics including tyrosine kinase inhibitors (TKIs) and neutralizing antibodies lack clinical efficacy, either alone or in combination. The major challenge is to uncover the genetic RTK alterations driving GBM initiation and progression, as well as to elucidate the mechanisms toward therapeutic resistance. In this review, we will discuss the genetic alterations in these 5 commonly targeted RTKs, the clinical trial outcomes of the associated RTK-targeting therapeutics, and the potential mechanisms toward the resistance. We anticipate that future design of new clinical trials with combination strategies, based on the genetic alterations within an individual patient's tumor and mechanisms contributing to therapeutic resistance after treatment, will achieve durable remissions and improve outcomes in GBM patients." @default.
• W3198986309 created "2021-09-27" @default.
• W3198986309 creator A5036251142 @default.
• W3198986309 creator A5039285511 @default.
• W3198986309 creator A5048925301 @default.
• W3198986309 creator A5069653639 @default.
• W3198986309 creator A5090868034 @default.
• W3198986309 date "2021-01-01" @default.
• W3198986309 modified "2023-10-14" @default.
• W3198986309 title "Receptor tyrosine kinases as druggable targets in glioblastoma: Do signaling pathways matter?" @default.
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