PMID- 22248929
OWN - NLM
STAT- MEDLINE
DCOM- 20120629
LR  - 20211203
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 2
IP  - 12
DP  - 2011 Dec
TI  - Will PI3K pathway inhibitors be effective as single agents in patients with 
      cancer?
PG  - 1314-21
AB  - The phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) 
      axis regulates essential cellular functions including cell survival, 
      proliferation, metabolism, migration, and angiogenesis. The PI3K pathway is 
      activated in human cancers by mutation, amplification, and deletion of genes 
      encoding components of this pathway. The critical role of PI3K in cancer has led 
      to the development of drugs targeting the effector mechanisms of this signaling 
      network. Recent studies have shown that inhibition at multiple levels of the PI3K 
      pathway results in FOXO-dependent feedback reactivation of several receptor 
      tyrosine kinases (RTKs) which, in turn, limit the sustained inhibition of this 
      pathway and attenuates the action of therapeutic antagonists. This suggests that 
      if used as single agents, PI3K pathway inhibitors may have limited clinical 
      activity. We propose herein that to successfully target the output of the PI3K 
      pathway in cancer cells, combination therapies that hinder these compensatory 
      mechanisms should be used. Thus, combination therapies that target RTKs, PI3K, 
      and mTOR activities may be required to maximize the clinical benefit derived from 
      treatment with these inhibitors.
FAU - Garrett, Joan T
AU  - Garrett JT
AD  - Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University, 
      Nashville, TN, USA.
FAU - Chakrabarty, Anindita
AU  - Chakrabarty A
FAU - Arteaga, Carlos L
AU  - Arteaga CL
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (Antineoplastic Agents)
RN  - 0 (FOXO1 protein, human)
RN  - 0 (Forkhead Box Protein O1)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
EIN - Oncotarget. 2018 Aug 17;9(64):32400. PMID: 30190795
MH  - Animals
MH  - Antineoplastic Agents/pharmacology
MH  - Forkhead Box Protein O1
MH  - Forkhead Transcription Factors/metabolism
MH  - Humans
MH  - Mice
MH  - Neoplasms/drug therapy/*metabolism/pathology
MH  - Phosphatidylinositol 3-Kinase/metabolism
MH  - *Phosphoinositide-3 Kinase Inhibitors
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Receptor Protein-Tyrosine Kinases/*metabolism
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC3282088
EDAT- 2012/01/18 06:00
MHDA- 2012/06/30 06:00
PMCR- 2011/12/01
CRDT- 2012/01/18 06:00
PHST- 2012/01/18 06:00 [entrez]
PHST- 2012/01/18 06:00 [pubmed]
PHST- 2012/06/30 06:00 [medline]
PHST- 2011/12/01 00:00 [pmc-release]
AID - 409 [pii]
AID - 10.18632/oncotarget.409 [doi]
PST - ppublish
SO  - Oncotarget. 2011 Dec;2(12):1314-21. doi: 10.18632/oncotarget.409.