Kinase-Targeted Therapies for Glioblastoma
Maria Salbini1, Alessia Formato1, Maria Patrizia Mongiardi1
1Institute of Biochemistry and Cell Biology, National Research Council, Via Ercole Ramarini 32, Monterotondo, 00015 Rome, Italy.
Abstract:
Protein phosphorylation and dephosphorylation are key mechanisms that regulate cellular activities. The addition or removal of phosphate groups by specific enzymes, known as kinases and phosphatases, activates or inhibits many enzymes and receptors involved in various cell signaling pathways. Dysregulated activity of these enzymes is associated with various diseases, predominantly cancers. Synthetic and natural single- and multiple-kinase inhibitors are currently being used as targeted therapies for different tumors, including glioblastoma. Glioblastoma IDH-wild-type is the most aggressive brain tumor in adults, with a median overall survival of 15 months. The great majority of glioblastoma patients present mutations in receptor tyrosine kinase (RTK) signaling pathways responsible for tumor initiation and/or progression. Despite this, the multi-kinase inhibitor regorafenib has only recently been approved for glioblastoma patients in some countries. In this review, we analyze the history of kinase inhibitor drugs in glioblastoma therapy.
Insights
Kinase inhibitors are crucial for treating glioblastoma, a deadly brain cancer. This review examines the history and development of these targeted therapies for glioblastoma patients.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Protein phosphorylation by kinases and phosphatases regulates cellular functions.
- Dysregulated kinase activity is linked to cancer, particularly glioblastoma.
- Receptor tyrosine kinase (RTK) pathway mutations are common in glioblastoma.
Purpose of the Study:
- To review the history of kinase inhibitor drugs in glioblastoma therapy.
- To highlight the role of targeted therapies in treating this aggressive brain tumor.
Main Methods:
- Literature review of kinase inhibitors and glioblastoma treatment.
- Analysis of historical data on drug development and approval.
- Examination of signaling pathways implicated in glioblastoma.
Main Results:
- Kinase inhibitors represent a significant advancement in glioblastoma treatment.
- Regorafenib, a multi-kinase inhibitor, has recently gained approval for glioblastoma.
- Targeted therapies aim to address RTK pathway dysregulation.
Conclusions:
- Kinase inhibitors have evolved as a vital therapeutic strategy for glioblastoma.
- Further research into kinase inhibitor mechanisms and combinations is warranted.
- Understanding the history of these drugs informs future glioblastoma treatment approaches.
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