RGD Reference Report - The molecular biology of endometrial cancers and the implications for pathogenesis, classification, and targeted therapies. - Rat Genome Database

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The molecular biology of endometrial cancers and the implications for pathogenesis, classification, and targeted therapies.

Authors: Bansal, N  Yendluri, V  Wenham, RM 
Citation: Bansal N, etal., Cancer Control. 2009 Jan;16(1):8-13.
RGD ID: 4143515
Pubmed: PMID:19078924   (View Abstract at PubMed)

BACKGROUND: Understanding and identifying molecular biology and genetics of endometrial cancer are central to the development of novel therapies. This article reviews the molecular basis for genesis of endometrial cancer with regard to pathogenesis, classification, and implications for targeted therapies. METHODS: Genes and cellular pathways that may have an important role in endometrial cancers, both endometrioid and nonendometrioid cancers, are identified. Recently studied drugs and potential future drugs that target some of these genes and pathways are reviewed. RESULTS: The most frequent genetic alteration of endometrioid endometrial cancer is PTEN. PI3CA and K-ras mutations are less common but are often associated with PTEN. Alterations in MLH1 and MSH6 are documented with microsatellite instability. Beta-catenin has a minor but significant association. Conversely, p53 mutation is more often associated with nonendometrioid cancer; others being inactivation of p16 and/or overexpression of HER-2/neu. Absence of E-cadherin is more often than not present in nonendometrioid cancers and is associated with poor prognosis. Novel agents that target the AKT-PI3K-mTOR pathway and those that inhibit epidermal growth factor receptor (EGFR), vascular endothelial growth factors (VEGF), fibroblast growth factor receptor 2 (FGFR2), and folate receptors are currently being investigated. CONCLUSIONS: Novel targeted agents, either alone or in combination with cytotoxic agents, may result in superior treatment for patients.



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)
ERBB2Humanaltered epidermal growth factor/neuregulin signaling pathway  TAS  RGD 
Erbb2Mousealtered epidermal growth factor/neuregulin signaling pathway  ISOERBB2 (Homo sapiens) RGD 
Erbb2Rataltered epidermal growth factor/neuregulin signaling pathway  ISOERBB2 (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 
MLH1Humanaltered mismatch repair pathway  TAS  RGD 
MSH6Humanaltered mismatch repair pathway  TAS  RGD 
Mlh1Mousealtered mismatch repair pathway  ISOMLH1 (Homo sapiens) RGD 
Mlh1Rataltered mismatch repair pathway  ISOMLH1 (Homo sapiens) RGD 
Msh6Mousealtered mismatch repair pathway  ISOMSH6 (Homo sapiens) RGD 
TP53Humanaltered p53 signaling pathway   TAS  RGD 
Tp53Rataltered p53 signaling pathway   ISOTP53 (Homo sapiens) RGD 
Trp53Mousealtered p53 signaling pathway   ISOTP53 (Homo sapiens) RGD 
PIK3CAHumanaltered phosphatidylinositol 3-kinase-Akt signaling pathway  TAS  RGD 
PTENHumanaltered phosphatidylinositol 3-kinase-Akt signaling pathway  TAS  RGD 
Pik3caMousealtered phosphatidylinositol 3-kinase-Akt signaling pathway  ISOPIK3CA (Homo sapiens) RGD 
Pik3caRataltered phosphatidylinositol 3-kinase-Akt signaling pathway  ISOPIK3CA (Homo sapiens) RGD 
PtenMousealtered phosphatidylinositol 3-kinase-Akt signaling pathway  ISOPTEN (Homo sapiens) RGD 
PtenRataltered phosphatidylinositol 3-kinase-Akt signaling pathway  ISOPTEN (Homo sapiens) RGD 
CTNNB1Humanaltered Wnt signaling, canonical pathway   TAS  RGD 
Ctnnb1Mousealtered Wnt signaling, canonical pathway   ISOCTNNB1 (Homo sapiens) RGD 
Ctnnb1Rataltered Wnt signaling, canonical pathway   ISOCTNNB1 (Homo sapiens) RGD 
CTNNB1Humanendometrial cancer pathway   TAS  RGD 
Ctnnb1Mouseendometrial cancer pathway   ISOCTNNB1 (Homo sapiens) RGD 
Ctnnb1Ratendometrial cancer pathway   ISOCTNNB1 (Homo sapiens) RGD 
ERBB2Humanendometrial cancer pathway   TAS  RGD 
Erbb2Mouseendometrial cancer pathway   ISOERBB2 (Homo sapiens) RGD 
Erbb2Ratendometrial cancer pathway   ISOERBB2 (Homo sapiens) RGD 
KRASHumanendometrial cancer pathway   TAS  RGD 
KrasMouseendometrial cancer pathway   ISOKRAS (Homo sapiens) RGD 
KrasRatendometrial cancer pathway   ISOKRAS (Homo sapiens) RGD 
MLH1Humanendometrial cancer pathway   TAS  RGD 
MSH6Humanendometrial cancer pathway   TAS  RGD 
Mlh1Mouseendometrial cancer pathway   ISOMLH1 (Homo sapiens) RGD 
Mlh1Ratendometrial cancer pathway   ISOMLH1 (Homo sapiens) RGD 
Msh6Mouseendometrial cancer pathway   ISOMSH6 (Homo sapiens) RGD 
PIK3CAHumanendometrial cancer pathway   TAS  RGD 
PTENHumanendometrial cancer pathway   TAS  RGD 
Pik3caMouseendometrial cancer pathway   ISOPIK3CA (Homo sapiens) RGD 
Pik3caRatendometrial cancer pathway   ISOPIK3CA (Homo sapiens) RGD 
PtenMouseendometrial cancer pathway   ISOPTEN (Homo sapiens) RGD 
PtenRatendometrial cancer pathway   ISOPTEN (Homo sapiens) RGD 
TP53Humanendometrial cancer pathway   TAS  RGD 
Tp53Ratendometrial cancer pathway   ISOTP53 (Homo sapiens) RGD 
Trp53Mouseendometrial cancer pathway   ISOTP53 (Homo sapiens) RGD 
Objects Annotated

Genes (Rattus norvegicus)
Ctnnb1  (catenin beta 1)
Erbb2  (erb-b2 receptor tyrosine kinase 2)
Kras  (KRAS proto-oncogene, GTPase)
Mlh1  (mutL homolog 1)
Pik3ca  (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha)
Pten  (phosphatase and tensin homolog)
Tp53  (tumor protein p53)

Genes (Mus musculus)
Ctnnb1  (catenin beta 1)
Erbb2  (erb-b2 receptor tyrosine kinase 2)
Kras  (Kirsten rat sarcoma viral oncogene homolog)
Mlh1  (mutL homolog 1)
Msh6  (mutS homolog 6)
Pik3ca  (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
Pten  (phosphatase and tensin homolog)
Trp53  (transformation related protein 53)

Genes (Homo sapiens)
CTNNB1  (catenin beta 1)
ERBB2  (erb-b2 receptor tyrosine kinase 2)
KRAS  (KRAS proto-oncogene, GTPase)
MLH1  (mutL homolog 1)
MSH6  (mutS homolog 6)
PIK3CA  (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
PTEN  (phosphatase and tensin homolog)
TP53  (tumor protein p53)


Additional Information