PMID- 33165737
OWN - NLM
STAT- MEDLINE
DCOM- 20210429
LR  - 20211204
IS  - 2095-0225 (Electronic)
IS  - 2095-0217 (Linking)
VI  - 15
IP  - 2
DP  - 2021 Apr
TI  - mTOR-targeted cancer therapy: great target but disappointing clinical outcomes, 
      why?
PG  - 221-231
LID - 10.1007/s11684-020-0812-7 [doi]
AB  - The mammalian target of rapamycin (mTOR) critically regulates several essential 
      biological functions, such as cell growth, metabolism, survival, and immune 
      response by forming two important complexes, namely, mTOR complex 1 (mTORC1) and 
      complex 2 (mTORC2). mTOR signaling is often dysregulated in cancers and has been 
      considered an attractive cancer therapeutic target. Great efforts have been made 
      to develop efficacious mTOR inhibitors, particularly mTOR kinase inhibitors, 
      which suppress mTORC1 and mTORC2; however, major success has not been achieved. 
      With the strong scientific rationale, the intriguing question is why cancers are 
      insensitive or not responsive to mTOR-targeted cancer therapy in clinics. Beyond 
      early findings on induced activation of PI3K/Akt, MEK/ERK, and Mnk/eIF4E survival 
      signaling pathways that compromise the efficacy of rapalog-based cancer therapy, 
      recent findings on the essential role of GSK3 in mediating cancer cell response 
      to mTOR inhibitors and mTORC1 inhibition-induced upregulation of PD-L1 in cancer 
      cells may provide some explanations. These new findings may also offer us the 
      opportunity to rationally utilize mTOR inhibitors in cancer therapy. Further 
      elucidation of the biology of complicated mTOR networks may bring us the hope to 
      develop effective therapeutic strategies with mTOR inhibitors against cancer.
FAU - Sun, Shi-Yong
AU  - Sun SY
AD  - Department of Hematology and Medical Oncology, Emory University School of 
      Medicine and Winship Cancer Institute, Atlanta, GA, 30322, USA. ssun@emory.edu.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20201109
PL  - China
TA  - Front Med
JT  - Frontiers of medicine
JID - 101549428
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
SB  - IM
MH  - Glycogen Synthase Kinase 3
MH  - Mechanistic Target of Rapamycin Complex 2
MH  - *Neoplasms/drug therapy
MH  - *Phosphatidylinositol 3-Kinases
MH  - Protein Kinase Inhibitors
MH  - Proto-Oncogene Proteins c-akt
MH  - TOR Serine-Threonine Kinases
OTO - NOTNLM
OT  - E3 ubiquitin ligase
OT  - GSK3
OT  - PD-L1
OT  - cancer therapy
OT  - mTOR
OT  - protein degradation
OT  - resistance
EDAT- 2020/11/10 06:00
MHDA- 2021/04/30 06:00
CRDT- 2020/11/09 14:27
PHST- 2020/05/06 00:00 [received]
PHST- 2020/06/12 00:00 [accepted]
PHST- 2020/11/10 06:00 [pubmed]
PHST- 2021/04/30 06:00 [medline]
PHST- 2020/11/09 14:27 [entrez]
AID - 10.1007/s11684-020-0812-7 [pii]
AID - 10.1007/s11684-020-0812-7 [doi]
PST - ppublish
SO  - Front Med. 2021 Apr;15(2):221-231. doi: 10.1007/s11684-020-0812-7. Epub 2020 Nov 
      9.