title: Genetic biomarkers of drug response for small-molecule therapeutics targeting the RTK/Ras/PI3K, p53 or Rb pathway in glioblastoma.
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.
authors.affiliation: Department of Neurosurgery, Brain Tumor Center of the Erasmus Medical Center, Rotterdam, The Netherlands.|UCL Cancer Institute, Paul O'Gorman Building, London, UK.
authors.forename: Subramanian
authors.initials: S
authors.lastname: Venkatesan
authors.affiliation: Department of Neurosurgery, Brain Tumor Center of the Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Martine L M
authors.initials: ML
authors.lastname: Lamfers
authors.affiliation: Department of Neurosurgery, Brain Tumor Center of the Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Clemens M F
authors.initials: CM
authors.lastname: Dirven
authors.affiliation: Department of Neurosurgery, Brain Tumor Center of the Erasmus Medical Center, Rotterdam, The Netherlands.|Department of Neurosurgery, Elisabeth Hospital, Tilburg, The Netherlands.
authors.forename: Sieger
authors.initials: S
authors.lastname: Leenstra
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005819:Genetic Markers; D005909:Glioblastoma / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D057285:Precision Medicine; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D054316:Biomarkers, Pharmacological; D005819:Genetic Markers; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020794:Receptor Protein-Tyrosine Kinases; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D018631:ras Proteins; C495901:TP53 protein, human
keywords: brain tumor; genetic biomarkers; glioblastoma; personalized medicine; resistance; small-molecule kinase inhibitors