PMID- 34944625
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211229
IS  - 2227-9059 (Print)
IS  - 2227-9059 (Electronic)
IS  - 2227-9059 (Linking)
VI  - 9
IP  - 12
DP  - 2021 Dec 1
TI  - The Bumpy Road towards mTOR Inhibition in Glioblastoma: Quo Vadis?
LID - 10.3390/biomedicines9121809 [doi]
LID - 1809
AB  - Glioblastoma multiforme (GBM), a grade IV astrocytoma, is a lethal brain tumor 
      with a poor prognosis. Despite recent advances in the molecular biology of GBM, 
      neuro-oncologists have very limited treatment options available to improve the 
      survival of GBM patients. A prominent signaling pathway implicated in GBM 
      pathogenesis is that of the mechanistic target of rapamycin (mTOR). Attempts to 
      target the mTOR pathway with first-generation mTOR inhibitors appeared promising 
      in the preclinical stage; however, results have been disappointing in clinical 
      trials, owing to the heterogeneous nature of GBM, escape mechanisms against 
      treatment, the blood-brain barrier, drug-related toxicities, and the imperfect 
      design of clinical trials, among others. The development of next-generation mTOR 
      inhibitors and their current evaluation in clinical trials have sparked new hope 
      to realize the clinical potential of mTOR inhibitors in GBM. Meanwhile, studies 
      are continuously furthering our understanding of mTOR signaling dysregulation, 
      its downstream effects, and interplay with other signaling pathways in GBM 
      tumors. Therefore, it remains to be seen whether targeting mTOR in GBM will 
      eventually prove to be fruitful or futile.
FAU - Papavassiliou, Kostas A
AU  - Papavassiliou KA
AUID- ORCID: 0000-0001-9620-745X
AD  - Department of Biological Chemistry, Medical School, National and Kapodistrian 
      University of Athens, 11527 Athens, Greece.
FAU - Papavassiliou, Athanasios G
AU  - Papavassiliou AG
AUID- ORCID: 0000-0001-5803-4527
AD  - Department of Biological Chemistry, Medical School, National and Kapodistrian 
      University of Athens, 11527 Athens, Greece.
LA  - eng
PT  - Journal Article
DEP - 20211201
PL  - Switzerland
TA  - Biomedicines
JT  - Biomedicines
JID - 101691304
PMC - PMC8698473
OTO - NOTNLM
OT  - glioblastoma multiforme
OT  - mTOR inhibitors
OT  - mTOR signaling
OT  - mTORC1
OT  - mTORC2
COIS- The authors declare no conflict of interest.
EDAT- 2021/12/25 06:00
MHDA- 2021/12/25 06:01
PMCR- 2021/12/01
CRDT- 2021/12/24 01:06
PHST- 2021/11/01 00:00 [received]
PHST- 2021/11/29 00:00 [revised]
PHST- 2021/11/30 00:00 [accepted]
PHST- 2021/12/24 01:06 [entrez]
PHST- 2021/12/25 06:00 [pubmed]
PHST- 2021/12/25 06:01 [medline]
PHST- 2021/12/01 00:00 [pmc-release]
AID - biomedicines9121809 [pii]
AID - biomedicines-09-01809 [pii]
AID - 10.3390/biomedicines9121809 [doi]
PST - epublish
SO  - Biomedicines. 2021 Dec 1;9(12):1809. doi: 10.3390/biomedicines9121809.