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.


Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
altered epidermal growth factor/neuregulin signaling pathway  TAS 5490965; 5490965; 5490965 RGD 
altered epidermal growth factor/neuregulin signaling pathway  ISOEGF (Homo sapiens)5490965; 5490965 RGD 
altered epidermal growth factor/neuregulin signaling pathway  ISOEGFR (Homo sapiens)5490965; 5490965 RGD 
altered epidermal growth factor/neuregulin signaling pathway  ISOTGFA (Homo sapiens)5490965; 5490965 RGD 
altered extracellular signal-regulated Raf/Mek/Erk signaling pathway  TAS 5490965 RGD 
altered extracellular signal-regulated Raf/Mek/Erk signaling pathway  ISOKRAS (Homo sapiens)5490965; 5490965 RGD 
altered Hedgehog signaling pathway  TAS 5490965 RGD 
altered Hedgehog signaling pathway  ISOSHH (Homo sapiens)5490965; 5490965 RGD 
altered phosphatidylinositol 3-kinase-Akt signaling pathway  TAS 5490965; 5490965 RGD 
altered phosphatidylinositol 3-kinase-Akt signaling pathway  ISOAKT2 (Homo sapiens)5490965; 5490965 RGD 
altered phosphatidylinositol 3-kinase-Akt signaling pathway  ISOPTEN (Homo sapiens)5490965; 5490965 RGD 
altered scatter factor/hepatocyte growth factor signaling pathway  TAS 5490965 RGD 
altered scatter factor/hepatocyte growth factor signaling pathway  ISOMET (Homo sapiens)5490965; 5490965 RGD 
altered transforming growth factor-beta Smad dependent signaling pathway   TAS 5490965; 5490965 RGD 
altered transforming growth factor-beta Smad dependent signaling pathway   ISOSMAD4 (Homo sapiens)5490965; 5490965 RGD 
altered transforming growth factor-beta Smad dependent signaling pathway   ISOTGFBR2 (Homo sapiens)5490965; 5490965 RGD 
pancreatic cancer pathway   TAS 5490965; 5490965; 5490965; 5490965; 5490965; 5490965; 5490965; 5490965; 5490965; 5490965 RGD 
pancreatic cancer pathway   ISOAKT2 (Homo sapiens)5490965; 5490965 RGD 
pancreatic cancer pathway   ISOEGF (Homo sapiens)5490965; 5490965 RGD 
pancreatic cancer pathway   ISOEGFR (Homo sapiens)5490965; 5490965 RGD 
pancreatic cancer pathway   ISOKRAS (Homo sapiens)5490965; 5490965 RGD 
pancreatic cancer pathway   ISOMET (Homo sapiens)5490965; 5490965 RGD 
pancreatic cancer pathway   ISOPTEN (Homo sapiens)5490965; 5490965 RGD 
pancreatic cancer pathway   ISOSHH (Homo sapiens)5490965; 5490965 RGD 
pancreatic cancer pathway   ISOSMAD4 (Homo sapiens)5490965; 5490965 RGD 
pancreatic cancer pathway   ISOTGFA (Homo sapiens)5490965; 5490965 RGD 
pancreatic cancer pathway   ISOTGFBR2 (Homo sapiens)5490965; 5490965 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