Abstract
Glioblastoma is the most deadly and frequently occurring primary malignant tumor of the central nervous system. Genomic studies have shown that mutated oncogenes and tumor suppressor genes in glioblastoma mainly occur in three pathways: the RTK/Ras/PI3K signaling, the p53 and the Rb pathways. In this review, we summarize the modulatory effects of genetic aberrations in these three pathways to drugs targeting these specific pathways. We also provide an overview of the preclinical efforts made to identify genetic biomarkers of response and resistance. Knowledge of biomarkers will finally promote patient stratification in clinical trials, a prerequisite for trial design in the era of precision medicine.
Keywords:
brain tumor; genetic biomarkers; glioblastoma; personalized medicine; resistance; small-molecule kinase inhibitors.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Antineoplastic Agents / therapeutic use*
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Biomarkers, Pharmacological*
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Brain Neoplasms / drug therapy*
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Brain Neoplasms / genetics*
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Drug Resistance, Neoplasm / genetics
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Genetic Markers
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Glioblastoma / drug therapy*
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Glioblastoma / genetics*
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Humans
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Molecular Targeted Therapy*
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Mutation
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphoinositide-3 Kinase Inhibitors
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Precision Medicine
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Receptor Protein-Tyrosine Kinases / antagonists & inhibitors
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Receptor Protein-Tyrosine Kinases / metabolism
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Retinoblastoma Protein / genetics
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Retinoblastoma Protein / metabolism
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Signal Transduction / drug effects
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / metabolism
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ras Proteins / metabolism
Substances
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Antineoplastic Agents
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Biomarkers, Pharmacological
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Genetic Markers
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Phosphoinositide-3 Kinase Inhibitors
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Retinoblastoma Protein
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TP53 protein, human
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Tumor Suppressor Protein p53
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Receptor Protein-Tyrosine Kinases
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ras Proteins