PMID- 21547565
OWN - NLM
STAT- MEDLINE
DCOM- 20111121
LR  - 20211020
IS  - 1776-260X (Electronic)
IS  - 1776-2596 (Linking)
VI  - 6
IP  - 2
DP  - 2011 Jun
TI  - Targeting phosphatidylinositol 3 kinase (PI3K)-Akt beyond rapalogs.
PG  - 103-17
LID - 10.1007/s11523-011-0176-7 [doi]
AB  - The activation of the phosphatidylinositol 3 kinase (PI3K)-Akt pathway is a known 
      causal mechanism of oncogenesis and resistance to cancer treatments. The process 
      of PI3K-Akt pathway activation is complex and includes receptor tyrosine 
      kinase(RTK) activation, PIK3CA mutations, loss of phosphatase and tensin homolog 
      (PTEN), Akt mutations, tuberous sclerosis complex (TSC) mutations, and Ras 
      homologue enriched in brain (RHEB) gene amplifications. The blockage of mammalian 
      target of rapamycin (mTOR), the key downstream pathway protein, has been 
      successful in selected cancer types, with mTOR-targeting agents available for 
      clinical use. Other novel drugs blocking this pathway such as PI3K inhibitors, 
      Akt inhibitors and PDK-1 inhibitors are currently only available for 
      investigational use, but have shown promise as cancer therapies in both 
      preclinical and early phase clinical studies. The newer generations of these 
      inhibitors are more specific and have improved potency and safety. The 
      combinations of targeted treatments against this pathway, blocking multiple 
      different steps, are under preliminary investigation. Further research is needed 
      to identify the biomarkers that predict treatment response and resistance in 
      order to optimize personalized medicine.
FAU - Ogita, Shin
AU  - Ogita S
AD  - Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA.
FAU - Lorusso, Patricia
AU  - Lorusso P
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20110506
PL  - France
TA  - Target Oncol
JT  - Targeted oncology
JID - 101270595
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.11.1 (Oncogene Protein v-akt)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Molecular Targeted Therapy/methods
MH  - Neoplasms/*drug therapy/*enzymology
MH  - Oncogene Protein v-akt/*antagonists & inhibitors/metabolism
MH  - Phosphatidylinositol 3-Kinase/metabolism
MH  - *Phosphoinositide-3 Kinase Inhibitors
MH  - Protein Kinase Inhibitors/*pharmacology/therapeutic use
MH  - Signal Transduction
MH  - Sirolimus/analogs & derivatives
EDAT- 2011/05/07 06:00
MHDA- 2011/12/13 00:00
CRDT- 2011/05/07 06:00
PHST- 2011/02/08 00:00 [received]
PHST- 2011/03/09 00:00 [accepted]
PHST- 2011/05/07 06:00 [entrez]
PHST- 2011/05/07 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
AID - 10.1007/s11523-011-0176-7 [doi]
PST - ppublish
SO  - Target Oncol. 2011 Jun;6(2):103-17. doi: 10.1007/s11523-011-0176-7. Epub 2011 May 
      6.