Tubulin targets in the pathobiology and therapy of glioblastoma multiforme. I. Class III beta-tubulin.
Glioblastoma multiforme (GBM) is the most common and deadliest form of primary brain cancer in adults. Despite advances in molecular biology and genetics of gliomas currently there is no effective treatment or promising molecularly targeted experimental therapeutic strategies for these tumors. In previous studies we have shown aberrant overexpression of the class III beta-tubulin isotype (betaIII-tubulin) in GBM and have proposed that this change may reflect perturbations in microtubule dynamics associated with glioma tumorigenesis, tumor progression and malignant transformation into GBM. This minireview focuses on microtubules and tubulin as emerging targets in potential therapy of GBM using a new class of betaIII-tubulin-targeted drugs in the light of recent developments concerning the function and potential role of this isotype in clinically aggressive tumor behavior, cancer stem cells, tumor hypoxia and chemoresistance to tubulin binding agents, principally taxanes.
Katsetos
Christos D
CD
Department of Pediatrics and Neurology, Drexel University College of Medicine and Section of Neurology, St Christopher's Hospital for Children, Philadelphia, Pennsylvania 19134, USA.
Dráberová
Eduarda
E
Legido
Agustin
A
Dumontet
Charles
C
Dráber
Pavel
P
D015415:Biomarkers / Q000378:metabolism; D015687:Cell Hypoxia / Q000502:physiology; D005909:Glioblastoma / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism*; D050257:Tubulin Modulators / Q000494:pharmacology / Q000627:therapeutic use*
D015415:Biomarkers; C498585:TUBB3 protein, human; D014404:Tubulin; D050257:Tubulin Modulators