Glioblastoma: therapeutic challenges, what lies ahead.
Glioblastoma (GBM) is one of the most aggressive human cancers. Despite current advances in multimodality therapies, such as surgery, radiotherapy and chemotherapy, the outcome for patients with high grade glioma remains fatal. The knowledge of how glioma cells develop and depend on the tumor environment might open opportunities for new therapies. There is now a growing awareness that the main limitations in understanding and successfully treating GBM might be bypassed by the identification of a distinct cell type that has defining properties of somatic stem cells, as well as cancer-initiating capacity - brain tumor stem cells, which could represent a therapeutic target. In addition, experimental studies have demonstrated that the combination of antiangiogenic therapy, based on the disruption of tumor blood vessels, with conventional chemotherapy generates encouraging results. Emerging reports have also shown that microglial cells can be used as therapeutic vectors to transport genes and/or substances to the tumor site, which opens up new perspectives for the development of GBM therapies targeting microglial cells. Finally, recent studies have shown that natural toxins can be conjugated to drugs that bind to overexpressed receptors in cancer cells, generating targeted-toxins to selectively kill cancer cells. These targeted-toxins are highly effective against radiation- and chemotherapy-resistant cancer cells, making them good candidates for clinical trials in GBM patients. In this review, we discuss recent studies that reveal new possibilities of GBM treatment taking into account cancer stem cells, angiogenesis, microglial cells and drug delivery in the development of new targeted-therapies.
Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Flavia R S
FR
Lima
Suzana Assad
SA
Kahn
Rossana C
RC
Soletti
Deborah
D
Biasoli
Tercia
T
Alves
Anna Carolina C
AC
da Fonseca
Celina
C
Garcia
Luciana
L
Romão
José
J
Brito
Rosenilde
R
Holanda-Afonso
Jane
J
Faria
Helena
H
Borges
Vivaldo
V
Moura-Neto
D001932:Brain Neoplasms / Q000188:drug therapy*; D016503:Drug Delivery Systems; D005909:Glioblastoma / Q000188:drug therapy*; D053823:Hedgehog Proteins / Q000502:physiology; D006801:Humans; D017628:Microglia / Q000502:physiology; D014411:Neoplastic Stem Cells / Q000187:drug effects; D034622:RNA Interference; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
D053823:Hedgehog Proteins; C509239:SHH protein, human; D042461:Vascular Endothelial Growth Factor A