Small molecule inhibitors in children with malignant gliomas.
Pediatric high grade gliomas (HGG) remain difficult to cure despite recent advances in imaging, neurosurgery, and radiation. Current treatment modalities have demonstrated only modest survival benefit. Research utilizing molecular biologic techniques reveals that the phenotype of HGG is complex and results from dysregulation of numerous inter-related cellular pathways. Knowledge of potential molecular targets along dysregulated pathways has led to the development of novel and highly specific targeted therapies, which include small molecule inhibitors. This article will review small molecule inhibition of cellular pathways involved in gliomagenesis, challenges to small molecule therapy, and future directions in the use of this therapy.
Herrington
Betty
B
Department of Pediatric Oncology, Dana-Farber Cancer Institute and Children's Hospital Boston, Boston, Massachusetts 02115, USA.
Kieran
Mark W
MW
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy*; D002648:Child; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005910:Glioma / Q000188:drug therapy*; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D018631:ras Proteins / Q000037:antagonists & inhibitors
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors; D017479:Receptors, Platelet-Derived Growth Factor; D018631:ras Proteins