PMID- 23605780
OWN - NLM
STAT- MEDLINE
DCOM- 20131023
LR  - 20211203
IS  - 1534-6269 (Electronic)
IS  - 1523-3790 (Linking)
VI  - 15
IP  - 4
DP  - 2013 Aug
TI  - Exploring novel therapeutic targets in GIST: focus on the PI3K/Akt/mTOR pathway.
PG  - 386-95
LID - 10.1007/s11912-013-0316-6 [doi]
AB  - Gastrointestinal stromal tumors (GISTs) are the most common soft tissue sarcoma, 
      and most feature abnormalities in two genes encoding the receptor tyrosine 
      kinases (RTKs), KIT, and PDGFRA. The RTK inhibitor imatinib revolutionized 
      treatment in GIST; however, drug resistance remains a challenge. Constitutive 
      autophosphorylation of RTKs is linked to phosphatidylinositol 3-kinase 
      (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway hyperactivation, which is 
      central to oncogenic signaling, and known to be dysregulated in GIST. Preclinical 
      experiments have confirmed that inhibiting the PI3K/Akt/mTOR pathway is a 
      rational target for therapy. Early studies using mTOR inhibitors have shown 
      limited success, which may be due to the activation of Akt that occurs following 
      mTORC1 inhibition. Therefore, targeting PI3K or Akt, which lie upstream of 
      mTORC1, may translate into more complete pathway inhibition. Several treatment 
      strategies are currently being developed in phase 1 and 2 clinical trials. 
      Compounds currently in development include pan-Class I PI3K inhibitors, dual 
      PI3K/mTOR inhibitors, and Akt inhibitors. The aim of this review is to highlight 
      the evidence for targeting PI3K/Akt/mTOR-dependent mechanisms in GIST and to 
      evaluate the existing preclinical and clinical data supporting this strategy.
FAU - Patel, Shreyaskumar
AU  - Patel S
AD  - The University of Texas M.D. Anderson Cancer Center, 1400 Holcombe Blvd, Unit 
      450, Houston, TX 77030, USA. spatel@mdanderson.org
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United States
TA  - Curr Oncol Rep
JT  - Current oncology reports
JID - 100888967
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - Gastrointestinal Neoplasms/*drug therapy
MH  - Gastrointestinal Stromal Tumors/*drug therapy
MH  - Humans
MH  - Molecular Targeted Therapy/methods
MH  - *Phosphoinositide-3 Kinase Inhibitors
MH  - Protein Kinase Inhibitors/*therapeutic use
MH  - Proto-Oncogene Proteins c-akt/*antagonists & inhibitors
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
EDAT- 2013/04/23 06:00
MHDA- 2013/10/24 06:00
CRDT- 2013/04/23 06:00
PHST- 2013/04/23 06:00 [entrez]
PHST- 2013/04/23 06:00 [pubmed]
PHST- 2013/10/24 06:00 [medline]
AID - 10.1007/s11912-013-0316-6 [doi]
PST - ppublish
SO  - Curr Oncol Rep. 2013 Aug;15(4):386-95. doi: 10.1007/s11912-013-0316-6.