Cancer Stem Cells in Glioblastoma: The Role of the mTOR Pathway

Abstract

Glioblastoma, the most aggressive type of primary brain tumor, portends a poor prognosis, despite current treatment modalities, due to recurrence of disease. Resistance to conventional therapies is caused by both extensive genetic abnormalities and dysregulation of the transcription landscape. A major cause of tumor recurrence, growth, and invasion is the presence of a unique population of cancer stem cells (CSCs) in the tumor and surrounding area. Consequently, CSCs have emerged as targets of interest in new treatment paradigms. The mechanistic target of rapamycin (mTOR), a serine/threonine kinase, forms two multiprotein complexes, mTORC1 and mTORC2, which regulate cell proliferation and migration. The pathogenesis of glioblastoma is largely due to the frequent loss of the tumor-suppressor gene phosphatase and tensin homolog (PTEN), leading to aberrant activation of the mTOR pathway in glioblastoma and its CSCs. Strategies to treat glioblastoma may involve inhibition of the mTOR pathway to target CSCs. Here, we explore the role of mTOR and related signaling pathways in the regulation of glioblastoma stem cells and define their roles as therapeutic targets in the treatment of glioblastoma.

Keywords: Glioblastoma; cancer stem cell; mTOR; mTORC1; mTORC2; review.