Cancer Stem Cells and Glioblastoma

Abstract

Gliomas are tumors of astroglial origin and the World health Organization (WHO) classifies them based on histological criteria into four grades of ascending malignancy. Glioblastoma multiforme (GBM, WHO grade IV) is among the most lethal of human cancers with conventional therapy offering only palliation. GBM accounts for the most frequent type of primary brain tumors in Europe and the USA, comprising more than a half of all gliomas, with a 5-year survival of patients of no more than 5 %. Despite concerted efforts and advances in currently available therapies, the expected survival of GBM patients remains dismal. Highly infiltrative character renders complete surgical resection impossible and together with notoriously known radio- and chemoresistance accounts for high recurrence rates and mortality of nearly 95 %. Traditionally, the approach to cancer treatment has been to eradicate all of the cancerous cells to achieve “cure” and was based on the idea that the vast majority of cells have tumorigenic potential. One reason for the lack of clinical advances is the lack of understanding of the GBM biology in general and the cellular origin of this disease in particular. The cancer stem cell hypothesis postulates that cancers contain a subset of highly aggressive cells that propagate and maintain the tumors through unlimited self-renewal and potent tumorigenicity. Within GBM, a distinct population of CD133⁺ cells has been documented to display stem cell properties in vitro, in particular self-renewal, unlimited proliferative potential, capacity for multi-lineage differentiation, and recapitulation of patient’s phenotype upon orthotopic implantation in immunocompromized host. The investigation and study of cancer stem cells received enormous attention over the past decade, yet it’s relevance to therapeutic resistance remains controversial. Although the cancer stem cell hypothesis may have multiple implications in therapeutic management of glioblastoma, as well as other brain tumor malignancies, caution must be exercised as targeting a rare population of tumorigenic cells without consideration of the largely heterogeneous tumor bulk comprised of proliferative cells may not change overall patient survival.