title: Current Therapeutic Alternatives and New Perspectives in Glioblastoma Multiforme.
abstract: BACKGROUND
  In the last two decades, there have been significant technological advances in the early detection of brain tumors. However, no notable improvements have been observed in the treatment of Glioblastoma Multiforme (GBM), the most common brain neoplasm coupled with the worst prognosis. GBM is characterized by an extensive resistance to a broad spectrum of anti-tumor drugs. This property is the result of a phenomenon known as Multiple Drug Resistance (MDR), which significantly limits noninvasive alternative therapies. This limitation is primarily due to the activity of ABC transporters and proteins related with DNA repair such as the MGMT enzyme. Due to the high mortality rate in GBM patients and current treatment deficits, new therapeutic strategies for this type of neoplasm are of vital importance.
  
  
  METHODS
  In this review, proposed treatments for GBM, including the use of alkylating agents with MGMT inhibitors, MDR modulators, and immunotherapies are discussed. We focused our bibliographic research on papers containing in vitro, in vivo, and clinical phase analysis published over the last 20 years.
  
  
  RESULTS
  Several studies have demonstrated good results using alkylating agents plus MGMT inhibitors, although without great improvements in survival. The use of modulators of ABC transporters enhances the effects of chemotherapy, proving it an effective complementary therapy. Immunotherapies have undergone significant developments as a directed and personalized approach for GBM treatment.
  
  
  CONCLUSIONS
  The use of alternative complementary therapies discussed in this review could increase the survival of GBM patients; however, additional clinical phase analysis and the generation of new treatment protocols are required.
authors.affiliation: Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivia. Chile.
authors.forename: Ángelo S T
authors.initials: ÁST
authors.lastname: Arévalo
authors.affiliation: Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivia. Chile.
authors.forename: José I
authors.initials: JI
authors.lastname: Erices
authors.affiliation: Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivia. Chile.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Uribe
authors.affiliation: King's College London, New Hunts House, Guys Campus, London. United Kingdom.
authors.forename: Jake
authors.initials: J
authors.lastname: Howden
authors.affiliation: Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivia. Chile.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Niechi
authors.affiliation: Servicio de Neurocirugía, Instituto de Neurocirugía Asenjo (inca), Santiago. Chile.
authors.forename: Sebastián
authors.initials: S
authors.lastname: Muñoz
authors.affiliation: Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivia. Chile.
authors.forename: Rody S
authors.initials: RS
authors.lastname: Martín
authors.affiliation: Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Campus Isla Teja s/n, P.O. Box: 567, Valdivia. Chile.
authors.forename: Claudia A Q
authors.initials: CAQ
authors.lastname: Monrás
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans
chemical_list: D000970:Antineoplastic Agents
keywords: Glioblastoma multiforme; MGMT; MRP-1; alkylating agents; immunotherapy; multiple drug resistance