Chemotherapy and target therapy in the management of adult high- grade gliomas

Curr Cancer Drug Targets. 2012 Oct;12(8):1016-31. doi: 10.2174/156800912803251207.

Abstract

Adult high grade gliomas (HGG) are the most frequent and fatal primary central nervous system (CNS) tumors. Despite recent advances in the knowledge of the pathology and the molecular features of this neoplasm, its prognosis remains poor. In the last years temozolomide (TMZ) has dramatically changed the life expectancy of these patients: the association of this drug with radiotherapy (RT), followed by TMZ alone, is the current standard of care. However, malignant gliomas often remain resistant to chemotherapy (CHT). Therefore, preclinical and clinical research efforts have been directed on identifying and understanding the different mechanisms of chemo-resistance operating in this subset of tumors,in order to develop effective strategies to overcome resistance. Moreover, the evidence of alterations in signal transduction pathways underlying tumor progression, has increased the number of trials investigating molecular target agents, such as anti-epidermal growth factor receptor (EGFR) and anti- vascular endothelial growth factor (VEGF) signaling. The purpose of this review is to point out the current standard of treatment and to explore new available target therapies in HGG.

Publication types

  • Review

MeSH terms

  • Adult
  • Angiogenesis Inhibitors / therapeutic use
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Central Nervous System Neoplasms / drug therapy*
  • Central Nervous System Neoplasms / metabolism
  • Central Nervous System Neoplasms / pathology
  • Cetuximab
  • DNA Modification Methylases / genetics
  • DNA Repair Enzymes / genetics
  • Dacarbazine / analogs & derivatives
  • Dacarbazine / therapeutic use
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / metabolism
  • Erlotinib Hydrochloride
  • Glioma / drug therapy*
  • Glioma / metabolism
  • Glioma / pathology
  • Humans
  • Nitrosourea Compounds / therapeutic use
  • Organophosphorus Compounds / therapeutic use
  • Promoter Regions, Genetic
  • Quinazolines / therapeutic use
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • Temozolomide
  • Tumor Suppressor Proteins / genetics

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Nitrosourea Compounds
  • Organophosphorus Compounds
  • Quinazolines
  • Tumor Suppressor Proteins
  • Dacarbazine
  • Erlotinib Hydrochloride
  • DNA Modification Methylases
  • MGMT protein, human
  • MTOR protein, human
  • EGFR protein, human
  • ErbB Receptors
  • TOR Serine-Threonine Kinases
  • DNA Repair Enzymes
  • fotemustine
  • Cetuximab
  • Temozolomide