Translational research in glioblastoma multiforme: molecular criteria for patient selection.
In spite of the dismal outcome of glioblastoma multiforme (GBM), we are in a position to provide a ray of hope to patients and families. Methylation of MGMT in tumor occurs in approximately a third of patients and predicts meaningful response and survival to adjuvant radiotherapy plus temozolomide. Limited access to tumor tissue in some patients could be circumvented by examining MGMT methylation in circulating serum DNA, although this approach needs to be validated. Molecular signatures are also promising prognostic and predictive markers, and clinical trials should be carried out to validate their use in the selection of patients for specific targeted therapies. Gene expression by quantitative PCR of key components of these molecular signatures could pave the way for easy identification of different subgroups of patients. Translational clinical trials are warranted in order to detect the subgroups of patients resistant to radiotherapy who may derive benefit from novel therapies, including antiangiogenic drugs.
Rosell
Rafael
R
Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Ctra Canyet, s/n, 08916 Barcelona, Spain. rrosell@ico.scs.es
de Las Peñas
Ramon
R
Balaña
Carme
C
Santarpia
Mariacarmela
M
Salazar
Fernanda
F
de Aguirre
Itziar
I
Reguart
Noemi
N
Villa
Salvador
S
Wei
Jia
J
Ramirez
Jose Luis
JL
Molina
Miguel Angel
MA
Ramon y Cajal
Santiago
S
Jablons
David
D
Taron
Miquel
M
D016543:Central Nervous System Neoplasms / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D004721:Endoplasmic Reticulum / Q000502:physiology; D000091342:Endoplasmic Reticulum Chaperone BiP; D005909:Glioblastoma / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D006360:Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D018832:Molecular Chaperones / Q000235:genetics; D018579:Patient Selection; D015398:Signal Transduction; D013234:Stem Cells; D051742:Transcription Factor CHOP / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics; D051153:Wnt Proteins / Q000502:physiology
C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D025521:Tumor Suppressor Proteins; D051153:Wnt Proteins; D051742:Transcription Factor CHOP; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes