RGD Reference Report - Antitumor activity of the combination of an HSP90 inhibitor and a PI3K/mTOR dual inhibitor against cholangiocarcinoma. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources
Advanced Search (OLGA)

Antitumor activity of the combination of an HSP90 inhibitor and a PI3K/mTOR dual inhibitor against cholangiocarcinoma.

Authors: Chen, Ming-Huang  Chiang, Kun-Chun  Cheng, Chi-Tung  Huang, Shih-Chiang  Chen, Yeng-Yang  Chen, Tsung-Wen  Yeh, Ta-Sen  Jan, Yi-Yin  Wang, Hsi-Ming  Weng, Jiang-Jie  Chang, Peter Mu-Hsin  Liu, Chun-Yu  Li, Chung-Pin  Chao, Yee  Chen, Ming-Han  Huang, Chi-Ying F  Yeh, Chun-Nan 
Citation: Chen MH, etal., Oncotarget. 2014 May 15;5(9):2372-89. doi: 10.18632/oncotarget.1706.
RGD ID: 152177907
Pubmed: PMID:24796583   (View Abstract at PubMed)
PMCID: PMC4058012   (View Article at PubMed Central)
DOI: DOI:10.18632/oncotarget.1706   (Journal Full-text)

The PI3K/Akt/mTOR pathway is overactivated and heat shock protein (HSP) 90 is overexpressed in common cancers. We hypothesized that targeting both pathways can kill intrahepatic cholangiocarcinoma (CCA) cells. HSP90 and PTEN protein expression was evaluated by immunohistochemical staining of samples from 78 patients with intrahepatic CCA. CCA cell lines and a thioacetamide (TAA)-induced CCA animal model were treated with NVP-AUY922 (an HSP90 inhibitor) and NVP-BEZ235 (a PI3K/mTOR inhibitor) alone or in combination. Both HSP90 overexpression and loss of PTEN were poor prognostic factors in patients with intrahepatic CCA. The combination of the HSP90 inhibitor NVP-AUY922 and the PI3K/mTOR inhibitor NVP-BEZ235 was synergistic in inducing cell death in CCA cells. A combination of NVP-AUY922 and NVP-BEZ235 caused tumor regression in CCA rat animal model. This combination not only inhibited the PI3K/Akt/mTOR pathway but also induced ROS, which may exacerbate the vicious cycle of ER stress. Our data suggest simultaneous targeting of the PI3K/mTOR and HSP pathways for CCA treatment.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
HSP90AA1Humanintrahepatic cholangiocarcinoma disease_progressionIEP protein:increased expression:liver (human)RGD 
HSP90AB1Humanintrahepatic cholangiocarcinoma disease_progressionIEP protein:increased expression:liver (human)RGD 
Hsp90aa1Ratintrahepatic cholangiocarcinoma disease_progressionISOHSP90AA1 (Homo sapiens)protein:increased expression:liver (human)RGD 
Hsp90aa1Mouseintrahepatic cholangiocarcinoma disease_progressionISOHSP90AA1 (Homo sapiens)protein:increased expression:liver (human)RGD 
Hsp90ab1Ratintrahepatic cholangiocarcinoma disease_progressionISOHSP90AB1 (Homo sapiens)protein:increased expression:liver (human)RGD 
Hsp90ab1Mouseintrahepatic cholangiocarcinoma disease_progressionISOHSP90AB1 (Homo sapiens)protein:increased expression:liver (human)RGD 
PTENHumanintrahepatic cholangiocarcinoma disease_progressionIEP protein:decreased expression:liver (human)RGD 
PtenRatintrahepatic cholangiocarcinoma disease_progressionISOPTEN (Homo sapiens)protein:decreased expression:liver (human)RGD 
PtenMouseintrahepatic cholangiocarcinoma disease_progressionISOPTEN (Homo sapiens)protein:decreased expression:liver (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hsp90aa1  (heat shock protein 90 alpha family class A member 1)
Hsp90ab1  (heat shock protein 90 alpha family class B member 1)
Pten  (phosphatase and tensin homolog)

Genes (Mus musculus)
Hsp90aa1  (heat shock protein 90, alpha (cytosolic), class A member 1)
Hsp90ab1  (heat shock protein 90 alpha (cytosolic), class B member 1)
Pten  (phosphatase and tensin homolog)

Genes (Homo sapiens)
HSP90AA1  (heat shock protein 90 alpha family class A member 1)
HSP90AB1  (heat shock protein 90 alpha family class B member 1)
PTEN  (phosphatase and tensin homolog)


Additional Information