PMID- 20639898
OWN - NLM
STAT- MEDLINE
DCOM- 20100917
LR  - 20220409
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Linking)
VI  - 29
IP  - 36
DP  - 2010 Sep 9
TI  - The role of signaling pathways in the development and treatment of hepatocellular 
      carcinoma.
PG  - 4989-5005
LID - 10.1038/onc.2010.236 [doi]
AB  - Hepatocellular carcinoma (HCC) is a highly prevalent, treatment-resistant 
      malignancy with a multifaceted molecular pathogenesis. Current evidence indicates 
      that during hepatocarcinogenesis, two main pathogenic mechanisms prevail: (1) 
      cirrhosis associated with hepatic regeneration after tissue damage caused by 
      hepatitis infection, toxins (for example, alcohol or aflatoxin) or metabolic 
      influences, and (2) mutations occurring in single or multiple oncogenes or tumor 
      suppressor genes. Both mechanisms have been linked with alterations in several 
      important cellular signaling pathways. These pathways are of interest from a 
      therapeutic perspective, because targeting them may help to reverse, delay or 
      prevent tumorigenesis. In this review, we explore some of the major pathways 
      implicated in HCC. These include the RAF/MEK/ERK pathway, phosphatidylinositol-3 
      kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway, WNT/beta-catenin 
      pathway, insulin-like growth factor pathway, hepatocyte growth factor/c-MET 
      pathway and growth factor-regulated angiogenic signaling. We focus on the role of 
      these pathways in hepatocarcinogenesis, how they are altered, and the 
      consequences of these abnormalities. In addition, we also review the latest 
      preclinical and clinical data on the rationally designed targeted agents that are 
      now being directed against these pathways, with early evidence of success.
FAU - Whittaker, S
AU  - Whittaker S
AD  - Dana-Farber Cancer Institute, Boston, MA, USA.
FAU - Marais, R
AU  - Marais R
FAU - Zhu, A X
AU  - Zhu AX
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20100719
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (HGF protein, human)
RN  - 0 (Somatomedins)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
RN  - EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor)
SB  - IM
MH  - Animals
MH  - Carcinoma, Hepatocellular/*etiology/genetics/pathology/*therapy
MH  - ErbB Receptors/genetics/physiology
MH  - Hepatocyte Growth Factor/genetics/physiology
MH  - Humans
MH  - Liver Neoplasms/*ethnology/*etiology/genetics/pathology/*therapy
MH  - MAP Kinase Signaling System/physiology
MH  - Models, Biological
MH  - Proto-Oncogene Proteins c-met/genetics/physiology
MH  - Receptors, Vascular Endothelial Growth Factor/genetics/physiology
MH  - Signal Transduction/genetics/*physiology
MH  - Somatomedins/genetics/physiology
RF  - 163
EDAT- 2010/07/20 06:00
MHDA- 2010/09/21 06:00
CRDT- 2010/07/20 06:00
PHST- 2010/07/20 06:00 [entrez]
PHST- 2010/07/20 06:00 [pubmed]
PHST- 2010/09/21 06:00 [medline]
AID - onc2010236 [pii]
AID - 10.1038/onc.2010.236 [doi]
PST - ppublish
SO  - Oncogene. 2010 Sep 9;29(36):4989-5005. doi: 10.1038/onc.2010.236. Epub 2010 Jul 
      19.