PMID- 21649577
OWN - NLM
STAT- MEDLINE
DCOM- 20110926
LR  - 20211203
IS  - 1875-533X (Electronic)
IS  - 0929-8673 (Linking)
VI  - 18
IP  - 18
DP  - 2011
TI  - Present and future of PI3K pathway inhibition in cancer: perspectives and 
      limitations.
PG  - 2674-85
AB  - Phosphoinositide 3-kinases (PI3Ks) control key signaling pathways in cancer 
      cells, leading to cell proliferation, survival, motility and angiogenesis. In 
      several human cancers, activation of PI3Ks results from gain-of-function or 
      over-expression of PI3Ks and/or hyperactivity of up- or downstream players in the 
      pathway. As inhibition of PI3Ks and downstream targets such as mammalian target 
      of rapamycin (mTOR) has been shown to reduce tumor growth in vitro and in 
      preclinical models, several small molecule inhibitors of PI3Ks are currently 
      undergoing clinical trial as novel agents in cancer therapy. These drugs include 
      inhibitors targeting all class I PI3Ks (alpha, beta, gamma, delta isoforms), compounds blocking 
      selective PI3K isoforms and dual inhibitors active on both PI3Ks and mTOR. 
      Herein, we summarize the pharmacology and preliminary clinical data of the main 
      PI3K inhibitors undergoing clinical trial. We will also review the preclinical 
      studies documenting the major effects of systemic PI3K inhibition on non-cancer 
      tissues, which have shed light on potential side effects, caveats and limitations 
      for PI3K blockade in patients.
FAU - Ciraolo, E
AU  - Ciraolo E
AD  - Department of Genetics, Biology and Biochemistry, Molecular Biotecnology Center, 
      University of Torino, Torino, Italy.
FAU - Morello, F
AU  - Morello F
FAU - Hirsch, E
AU  - Hirsch E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United Arab Emirates
TA  - Curr Med Chem
JT  - Current medicinal chemistry
JID - 9440157
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Protein Isoforms)
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Antineoplastic Agents/chemistry/metabolism/*therapeutic use
MH  - Clinical Medicine/*methods/trends
MH  - Humans
MH  - Neoplasms/*drug therapy/enzymology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - *Phosphoinositide-3 Kinase Inhibitors
MH  - Protein Isoforms/antagonists & inhibitors/metabolism
MH  - Protein Kinase Inhibitors/chemistry/metabolism/*therapeutic use
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/metabolism
EDAT- 2011/06/09 06:00
MHDA- 2011/09/29 06:00
CRDT- 2011/06/09 06:00
PHST- 2011/02/15 00:00 [received]
PHST- 2011/05/15 00:00 [accepted]
PHST- 2011/06/09 06:00 [entrez]
PHST- 2011/06/09 06:00 [pubmed]
PHST- 2011/09/29 06:00 [medline]
AID - BSP/CMC/E-Pub/2011/ 180 [pii]
AID - 10.2174/092986711796011193 [doi]
PST - ppublish
SO  - Curr Med Chem. 2011;18(18):2674-85. doi: 10.2174/092986711796011193.