RGD Reference Report - Pancreatic cancer: molecular pathogenesis and new therapeutic targets. - Rat Genome Database

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Pancreatic cancer: molecular pathogenesis and new therapeutic targets.

Authors: Wong, HH  Lemoine, NR 
Citation: Wong HH and Lemoine NR, Nat Rev Gastroenterol Hepatol. 2009 Jul;6(7):412-22. Epub 2009 Jun 9.
RGD ID: 5490965
Pubmed: PMID:19506583   (View Abstract at PubMed)
PMCID: PMC2882232   (View Article at PubMed Central)
DOI: DOI:10.1038/nrgastro.2009.89   (Journal Full-text)

Patients with pancreatic cancer normally present with advanced disease that is lethal and notoriously difficult to treat. Survival has not improved dramatically despite routine use of chemotherapy and radiotherapy; this situation signifies an urgent need for novel therapeutic approaches. Over the past decade, a large number of studies have been published that aimed to target the molecular abnormalities implicated in pancreatic tumor growth, invasion, metastasis, angiogenesis and resistance to apoptosis. This research is of particular importance, as data suggest that a large number of genetic alterations affect only a few major signaling pathways and processes involved in pancreatic tumorigenesis. Although laboratory results of targeted therapies have been impressive, until now only erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has demonstrated modest survival benefit in combination with gemcitabine in a phase III clinical trial. Whilst the failures of targeted therapies in the clinical setting are discouraging, lessons have been learnt and new therapeutic targets that hold promise for the future management of the disease are continuously emerging. This Review describes some of the important developments and targeted agents for pancreatic cancer that have been tested in clinical trials.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations


  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
EGFHumanaltered epidermal growth factor/neuregulin signaling pathway  TAS  RGD 
EGFRHumanaltered epidermal growth factor/neuregulin signaling pathway  TAS  RGD 
EgfMousealtered epidermal growth factor/neuregulin signaling pathway  ISOEGF (Homo sapiens) RGD 
EgfRataltered epidermal growth factor/neuregulin signaling pathway  ISOEGF (Homo sapiens) RGD 
EgfrMousealtered epidermal growth factor/neuregulin signaling pathway  ISOEGFR (Homo sapiens) RGD 
EgfrRataltered epidermal growth factor/neuregulin signaling pathway  ISOEGFR (Homo sapiens) RGD 
TGFAHumanaltered epidermal growth factor/neuregulin signaling pathway  TAS  RGD 
TgfaRataltered epidermal growth factor/neuregulin signaling pathway  ISOTGFA (Homo sapiens) RGD 
TgfaMousealtered epidermal growth factor/neuregulin signaling pathway  ISOTGFA (Homo sapiens) RGD 
KRASHumanaltered extracellular signal-regulated Raf/Mek/Erk signaling pathway  TAS  RGD 
KrasMousealtered extracellular signal-regulated Raf/Mek/Erk signaling pathway  ISOKRAS (Homo sapiens) RGD 
KrasRataltered extracellular signal-regulated Raf/Mek/Erk signaling pathway  ISOKRAS (Homo sapiens) RGD 
SHHHumanaltered Hedgehog signaling pathway  TAS  RGD 
ShhMousealtered Hedgehog signaling pathway  ISOSHH (Homo sapiens) RGD 
ShhRataltered Hedgehog signaling pathway  ISOSHH (Homo sapiens) RGD 
AKT2Humanaltered phosphatidylinositol 3-kinase-Akt signaling pathway  TAS  RGD 
Akt2Mousealtered phosphatidylinositol 3-kinase-Akt signaling pathway  ISOAKT2 (Homo sapiens) RGD 
Akt2Rataltered phosphatidylinositol 3-kinase-Akt signaling pathway  ISOAKT2 (Homo sapiens) RGD 
PTENHumanaltered phosphatidylinositol 3-kinase-Akt signaling pathway  TAS  RGD 
PtenMousealtered phosphatidylinositol 3-kinase-Akt signaling pathway  ISOPTEN (Homo sapiens) RGD 
PtenRataltered phosphatidylinositol 3-kinase-Akt signaling pathway  ISOPTEN (Homo sapiens) RGD 
METHumanaltered scatter factor/hepatocyte growth factor signaling pathway  TAS  RGD 
MetMousealtered scatter factor/hepatocyte growth factor signaling pathway  ISOMET (Homo sapiens) RGD 
MetRataltered scatter factor/hepatocyte growth factor signaling pathway  ISOMET (Homo sapiens) RGD 
SMAD4Humanaltered transforming growth factor-beta Smad dependent signaling pathway   TAS  RGD 
Smad4Rataltered transforming growth factor-beta Smad dependent signaling pathway   ISOSMAD4 (Homo sapiens) RGD 
Smad4Mousealtered transforming growth factor-beta Smad dependent signaling pathway   ISOSMAD4 (Homo sapiens) RGD 
TGFBR2Humanaltered transforming growth factor-beta Smad dependent signaling pathway   TAS  RGD 
Tgfbr2Rataltered transforming growth factor-beta Smad dependent signaling pathway   ISOTGFBR2 (Homo sapiens) RGD 
Tgfbr2Mousealtered transforming growth factor-beta Smad dependent signaling pathway   ISOTGFBR2 (Homo sapiens) RGD 
AKT2Humanpancreatic cancer pathway   TAS  RGD 
Akt2Mousepancreatic cancer pathway   ISOAKT2 (Homo sapiens) RGD 
Akt2Ratpancreatic cancer pathway   ISOAKT2 (Homo sapiens) RGD 
EGFHumanpancreatic cancer pathway   TAS  RGD 
EGFRHumanpancreatic cancer pathway   TAS  RGD 
EgfMousepancreatic cancer pathway   ISOEGF (Homo sapiens) RGD 
EgfRatpancreatic cancer pathway   ISOEGF (Homo sapiens) RGD 
EgfrMousepancreatic cancer pathway   ISOEGFR (Homo sapiens) RGD 
EgfrRatpancreatic cancer pathway   ISOEGFR (Homo sapiens) RGD 
KRASHumanpancreatic cancer pathway   TAS  RGD 
KrasMousepancreatic cancer pathway   ISOKRAS (Homo sapiens) RGD 
KrasRatpancreatic cancer pathway   ISOKRAS (Homo sapiens) RGD 
METHumanpancreatic cancer pathway   TAS  RGD 
MetMousepancreatic cancer pathway   ISOMET (Homo sapiens) RGD 
MetRatpancreatic cancer pathway   ISOMET (Homo sapiens) RGD 
PTENHumanpancreatic cancer pathway   TAS  RGD 
PtenMousepancreatic cancer pathway   ISOPTEN (Homo sapiens) RGD 
PtenRatpancreatic cancer pathway   ISOPTEN (Homo sapiens) RGD 
SHHHumanpancreatic cancer pathway   TAS  RGD 
SMAD4Humanpancreatic cancer pathway   TAS  RGD 
ShhMousepancreatic cancer pathway   ISOSHH (Homo sapiens) RGD 
ShhRatpancreatic cancer pathway   ISOSHH (Homo sapiens) RGD 
Smad4Mousepancreatic cancer pathway   ISOSMAD4 (Homo sapiens) RGD 
Smad4Ratpancreatic cancer pathway   ISOSMAD4 (Homo sapiens) RGD 
TGFAHumanpancreatic cancer pathway   TAS  RGD 
TGFBR2Humanpancreatic cancer pathway   TAS  RGD 
TgfaRatpancreatic cancer pathway   ISOTGFA (Homo sapiens) RGD 
TgfaMousepancreatic cancer pathway   ISOTGFA (Homo sapiens) RGD 
Tgfbr2Ratpancreatic cancer pathway   ISOTGFBR2 (Homo sapiens) RGD 
Tgfbr2Mousepancreatic cancer pathway   ISOTGFBR2 (Homo sapiens) RGD 
Objects Annotated

Genes (Rattus norvegicus)
Akt2  (AKT serine/threonine kinase 2)
Egf  (epidermal growth factor)
Egfr  (epidermal growth factor receptor)
Kras  (KRAS proto-oncogene, GTPase)
Met  (MET proto-oncogene, receptor tyrosine kinase)
Pten  (phosphatase and tensin homolog)
Shh  (sonic hedgehog signaling molecule)
Smad4  (SMAD family member 4)
Tgfa  (transforming growth factor alpha)
Tgfbr2  (transforming growth factor, beta receptor 2)

Genes (Mus musculus)
Akt2  (thymoma viral proto-oncogene 2)
Egf  (epidermal growth factor)
Egfr  (epidermal growth factor receptor)
Kras  (Kirsten rat sarcoma viral oncogene homolog)
Met  (met proto-oncogene)
Pten  (phosphatase and tensin homolog)
Shh  (sonic hedgehog)
Smad4  (SMAD family member 4)
Tgfa  (transforming growth factor alpha)
Tgfbr2  (transforming growth factor, beta receptor II)

Genes (Homo sapiens)
AKT2  (AKT serine/threonine kinase 2)
EGF  (epidermal growth factor)
EGFR  (epidermal growth factor receptor)
KRAS  (KRAS proto-oncogene, GTPase)
MET  (MET proto-oncogene, receptor tyrosine kinase)
PTEN  (phosphatase and tensin homolog)
SHH  (sonic hedgehog signaling molecule)
SMAD4  (SMAD family member 4)
TGFA  (transforming growth factor alpha)
TGFBR2  (transforming growth factor beta receptor 2)


Additional Information