PMID- 33066449
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201103
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 12
IP  - 10
DP  - 2020 Oct 14
TI  - Therapeutic Potential of PI3K/AKT/mTOR Pathway in Gastrointestinal Stromal 
      Tumors: Rationale and Progress.
LID - 10.3390/cancers12102972 [doi]
LID - 2972
AB  - Gastrointestinal stromal tumor (GIST) originates from interstitial cells of Cajal 
      (ICCs) in the myenteric plexus of the gastrointestinal tract. Most GISTs arise 
      due to mutations of KIT and PDGFRA gene activation, encoding the receptor 
      tyrosine kinase (RTK). The clinical use of the RTK inhibitor imatinib has 
      significantly improved the management of GIST patients; however, imatinib 
      resistance remains a challenge. The phosphatidylinositol 3-kinase (PI3K)/protein 
      kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is a critical 
      survival pathway for cell proliferation, apoptosis, autophagy and translation in 
      neoplasms. Constitutive autophosphorylation of RTKs has an impact on the 
      activation of the PI3K/AKT/mTOR pathway. In several preclinical and early-stage 
      clinical trials PI3K/AKT/mTOR signaling inhibition has been considered as a 
      promising targeted therapy strategy for GISTs. Various inhibitory drugs targeting 
      different parts of the PI3K/AKT/mTOR pathway are currently being investigated in 
      phase I and phase II clinical trials. This review highlights the progress for 
      PI3K/AKT/mTOR-dependent mechanisms in GISTs, and explores the relationship 
      between mTOR downstream signals, in particular, eukaryotic initiation factors 
      (eIFs) and the development of GISTs, which may be instrumental for identifying 
      novel therapeutic targets.
FAU - Duan, Yi
AU  - Duan Y
AD  - Department of Pathology, the Affiliated Hospital of Southwest Medical University, 
      Luzhou 646000, China.
FAU - Haybaeck, Johannes
AU  - Haybaeck J
AD  - Department of Pathology, Neuropathology and Molecular Pathology, Medical 
      University of Innsbruck, 6020 Innsbruck, Austria.
AD  - Diagnostic & Research Center for Molecular BioMedicine, Institute of Pathology, 
      Medical University of Graz, 8010 Graz, Austria.
FAU - Yang, Zhihui
AU  - Yang Z
AD  - Department of Pathology, the Affiliated Hospital of Southwest Medical University, 
      Luzhou 646000, China.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20201014
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC7602170
OTO - NOTNLM
OT  - PI3K/AKT/mTOR
OT  - eIFs
OT  - gastrointestinal stromal tumors
OT  - inhibitor
COIS- The authors declare no conflict of interest.
EDAT- 2020/10/18 06:00
MHDA- 2020/10/18 06:01
PMCR- 2020/10/14
CRDT- 2020/10/17 01:04
PHST- 2020/09/06 00:00 [received]
PHST- 2020/10/03 00:00 [revised]
PHST- 2020/10/12 00:00 [accepted]
PHST- 2020/10/17 01:04 [entrez]
PHST- 2020/10/18 06:00 [pubmed]
PHST- 2020/10/18 06:01 [medline]
PHST- 2020/10/14 00:00 [pmc-release]
AID - cancers12102972 [pii]
AID - cancers-12-02972 [pii]
AID - 10.3390/cancers12102972 [doi]
PST - epublish
SO  - Cancers (Basel). 2020 Oct 14;12(10):2972. doi: 10.3390/cancers12102972.