Park2019 - Cetuximab resistance in colorectal cancer

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Model Identifier
MODEL1909300004
Short description

It's an experimental + mathematical paper explaining probable targets for Cetixumab resistance in colorectal cancer.
Format
SBML (L2V4)
Related Publication
  • Systems analysis identifies potential target genes to overcome cetuximab resistance in colorectal cancer cells.
  • Park SM, Hwang CY, Cho SH, Lee D, Gong JR, Lee S, Nam S, Cho KH
  • The FEBS journal , 4/ 2019 , Volume 286 , Issue 7 , pages: 1305-1318 , PubMed ID: 30719834
  • Laboratory for Systems Biology and Bio-inspired Engineering, Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
  • Cetuximab (CTX), a monoclonal antibody against epidermal growth factor receptor, is being widely used for colorectal cancer (CRC) with wild-type (WT) KRAS. However, its responsiveness is still very limited and WT KRAS is not enough to indicate such responsiveness. Here, by analyzing the gene expression data of CRC patients treated with CTX monotherapy, we have identified DUSP4, ETV5, GNB5, NT5E, and PHLDA1 as potential targets to overcome CTX resistance. We found that knockdown of any of these five genes can increase CTX sensitivity in KRAS WT cells. Interestingly, we further found that GNB5 knockdown can increase CTX sensitivity even for KRAS mutant cells. We unraveled that GNB5 overexpression contributes to CTX resistance by modulating the Akt signaling pathway from experiments and mathematical simulation. Overall, these results indicate that GNB5 might be a promising target for combination therapy with CTX irrespective of KRAS mutation.
Contributors
Submitter of the first revision: Krishna Kumar Tiwari
Submitter of this revision: Krishna Kumar Tiwari
Modellers: Krishna Kumar Tiwari

Metadata information

isDescribedBy (1 statement)
PubMed 30719834

Curation status
Non-curated
Tags
Oncology

Connected external resources

SBGN view in Newt Editor

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Model files
Park2019.xml SBML L2V4 file for Park2019 model 59.58 KB Preview | Download

Additional files
Park2019.cps COPASI 4.27 (Build 217) file for Park2019 model 117.47 KB Preview | Download
Park2019.sedml SEDML file for Park2019 model 9.46 KB Preview | Download

  • Model originally submitted by : Krishna Kumar Tiwari
  • Submitted: Sep 30, 2019 3:24:14 PM
  • Last Modified: Sep 30, 2019 3:28:45 PM
Revisions
  • Version: 4 public model Download this version
    • Submitted on: Sep 30, 2019 3:28:45 PM
    • Submitted by: Krishna Kumar Tiwari
    • With comment: Edited model metadata online.
  • Version: 2 public model Download this version
    • Submitted on: Sep 30, 2019 3:24:14 PM
    • Submitted by: Krishna Kumar Tiwari
    • With comment: Edited model metadata online.

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