Background: Glioblastoma multiforme (GBM) continues to devastate patients and outfox
investigators and clinicians despite the preponderance of research directed at its biology, pathogenesis
and therapeutic advances. GBM routinely outlasts multidisciplinary treatment protocols, almost inevitably
recurring in a yet more aggressive and resistant form with distinct genetic differences from
the original tumor. Attempts to glean further insight into GBM point increasingly toward a subpopulation
of cells with a stem-like phenotype. These cancer stem cells, similar to those now described in
a variety of malignancies, are capable of tumorigenesis from a population of susceptible cells.
Conclusions: Glioma stem cells have thus become a prevalent focus in GBM research for their presumed
role in development, maintenance and recurrence of tumors. Glioma stem cells infiltrate the
white matter surrounding tumors and often evade resection. They are uniquely suited both biochemically
and environmentally to resist the best therapy currently available, intrinsically and efficiently
resistant to standard chemo- and radiotherapy. These stem cells create an extremely heterogenous
tumor that to date has had an answer for every therapeutic question, with continued dismal patient
survival. Targeting this population of glioma stem cells may hold the long-awaited key to durable
therapeutic efficacy in GBM.