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Targeting mTOR in Glioblastoma: Rationale and Preclinical/Clinical Evidence.
- Source :
-
Disease markers [Dis Markers] 2018 Dec 18; Vol. 2018, pp. 9230479. Date of Electronic Publication: 2018 Dec 18 (Print Publication: 2018). - Publication Year :
- 2018
-
Abstract
- The mechanistic target of rapamycin (mTOR) drives several physiologic and pathologic cellular processes and is frequently deregulated in different types of tumors, including glioblastoma (GBM). Despite recent advancements in understanding the molecular mechanisms involved in GBM biology, the survival rates of this tumor are still disappointing, primarily due to the lack of efficacious treatments. The phosphatase and tensin homolog (PTEN)/phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mTOR pathway has emerged as a crucial player in GBM development and progression. However, to date, all the attempts to target this pathway with PI3K, AKT, or mTORC1 inhibitors failed to improve the outcome of patients with GBM. Despite these discouraging results, recent evidence pointed out that the blockade of mTORC2 might provide a useful therapeutic strategy for GBM, with the potential to overcome the limitations that mTORC1 inhibitors have shown so far. In this review, we analyzed the rationale of targeting mTOR in GBM and the available preclinical and clinical evidence supporting the choice of this therapeutic approach, highlighting the different roles of mTORC1 and mTORC2 in GBM biology.
- Subjects :
- Animals
Antineoplastic Agents pharmacology
Antineoplastic Agents therapeutic use
Brain Neoplasms drug therapy
Evidence-Based Medicine
Glioblastoma drug therapy
Humans
Mechanistic Target of Rapamycin Complex 1 antagonists & inhibitors
Mechanistic Target of Rapamycin Complex 2 antagonists & inhibitors
Molecular Targeted Therapy
Signal Transduction drug effects
Brain Neoplasms metabolism
Glioblastoma metabolism
Mechanistic Target of Rapamycin Complex 1 metabolism
Mechanistic Target of Rapamycin Complex 2 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1875-8630
- Volume :
- 2018
- Database :
- MEDLINE
- Journal :
- Disease markers
- Publication Type :
- Academic Journal
- Accession number :
- 30662577
- Full Text :
- https://doi.org/10.1155/2018/9230479