PMID- 19384426
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20110714
LR  - 20220310
IS  - 1389-2029 (Print)
IS  - 1875-5488 (Electronic)
IS  - 1389-2029 (Linking)
VI  - 8
IP  - 5
DP  - 2007 Aug
TI  - The phosphoinositide 3-kinase pathway in human cancer: genetic alterations and 
      therapeutic implications.
PG  - 271-306
LID - 10.2174/138920207782446160 [doi]
AB  - The phosphoinositide 3-kinase (PI3K) pathway is frequently activated in human 
      cancer and represents an attractive target for therapies based on small molecule 
      inhibitors. PI3K isoforms play an essential role in the signal transduction 
      events activated by cell surface receptors including receptor tyrosine kinases 
      (RTKs) and G-protein-coupled receptors (GPCRs). There are eight known PI3K 
      isoforms in humans, which have been subdivided into three classes (I-III). 
      Therefore PI3Ks show considerable diversity and it remains unclear which kinases 
      in this family should be targeted in cancer. The class I(A) of PI3K comprises the 
      p110alpha, p110beta and p110delta isoforms, which associate with activated RTKs. 
      In human cancer, recent reports have described activating mutations in the PIK3CA 
      gene encoding p110alpha, and inactivating mutations in the phosphatase and tensin 
      homologue (PTEN) gene, a tumour suppressor and antagonist of the PI3K pathway. 
      The PIK3CA mutations described in cancer constitutively activate p110alpha and, 
      when expressed in cells drive oncogenic transformation. Moreover, these mutations 
      cause the constitutive activation of downstream signaling molecules such as 
      Akt/protein kinase B (PKB), mammalian target of rapamycin (mTOR) and ribosomal 
      protein S6 kinase (S6K) that is commonly observed in cancer cells. In addition to 
      p110alpha, the other isoforms of the PI3K family may also play a role in human 
      cancer, although their individual functions remain to be precisely identified. In 
      this review we will discuss the evidence implicating individual PI3K isoforms in 
      human cancer and their potential as drug targets in this context.
FAU - Arcaro, Alexandre
AU  - Arcaro A
AD  - Division of Clinical Chemistry and Biochemistry, University Children's Hospital 
      Zurich, Steinwiesstrasse 75, CH-8032 Zurich, Switzerland.
FAU - Guerreiro, Ana S
AU  - Guerreiro AS
LA  - eng
PT  - Journal Article
PL  - United Arab Emirates
TA  - Curr Genomics
JT  - Current genomics
JID - 100960527
PMC - PMC2652403
EDAT- 2007/08/01 00:00
MHDA- 2007/08/01 00:01
PMCR- 2008/02/01
CRDT- 2009/04/23 09:00
PHST- 2007/07/31 00:00 [received]
PHST- 2007/09/22 00:00 [revised]
PHST- 2007/09/25 00:00 [accepted]
PHST- 2009/04/23 09:00 [entrez]
PHST- 2007/08/01 00:00 [pubmed]
PHST- 2007/08/01 00:01 [medline]
PHST- 2008/02/01 00:00 [pmc-release]
AID - CG-8-271 [pii]
AID - 10.2174/138920207782446160 [doi]
PST - ppublish
SO  - Curr Genomics. 2007 Aug;8(5):271-306. doi: 10.2174/138920207782446160.