Tortolina2015 - Multiple signalling pathway associated with colorectal cancer

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  • Advances in dynamic modeling of colorectal cancer signaling-network regions, a path toward targeted therapies.
  • Tortolina L, Duffy DJ, Maffei M, Castagnino N, Carmody AM, Kolch W, Kholodenko BN, De Ambrosi C, Barla A, Biganzoli EM, Nencioni A, Patrone F, Ballestrero A, Zoppoli G, Verri A, Parodi S
  • Oncotarget , 3/ 2015 , Volume 6 , pages: 5041-5058 , PubMed ID: 25671297
  • Department of Informatics, Bioengineering, Robotics and Systems Engineering (DIBRIS), University of Genoa, Italy.
  • The interconnected network of pathways downstream of the TGFβ, WNT and EGF-families of receptor ligands play an important role in colorectal cancer pathogenesis.We studied and implemented dynamic simulations of multiple downstream pathways and described the section of the signaling network considered as a Molecular Interaction Map (MIM). Our simulations used Ordinary Differential Equations (ODEs), which involved 447 reactants and their interactions.Starting from an initial "physiologic condition", the model can be adapted to simulate individual pathologic cancer conditions implementing alterations/mutations in relevant onco-proteins. We verified some salient model predictions using the mutated colorectal cancer lines HCT116 and HT29. We measured the amount of MYC and CCND1 mRNAs and AKT and ERK phosphorylated proteins, in response to individual or combination onco-protein inhibitor treatments. Experimental and simulation results were well correlated. Recent independently published results were also predicted by our model.Even in the presence of an approximate and incomplete signaling network information, a predictive dynamic modeling seems already possible. An important long term road seems to be open and can be pursued further, by incremental steps, toward even larger and better parameterized MIMs. Personalized treatment strategies with rational associations of signaling-proteins inhibitors, could become a realistic goal.
Submitter of the first revision: Vijayalakshmi Chelliah
Submitter of this revision: Vijayalakshmi Chelliah
Modellers: Vijayalakshmi Chelliah

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BioModels Database MODEL1601250000

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Mathematical Modelling Ontology Ordinary differential equation model

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  • Model originally submitted by : Vijayalakshmi Chelliah
  • Submitted: Jan 25, 2016 4:53:26 PM
  • Last Modified: Feb 16, 2016 4:24:09 PM
  • Version: 2 public model Download this version
    • Submitted on: Feb 16, 2016 4:24:09 PM
    • Submitted by: Vijayalakshmi Chelliah
    • With comment: Current version of Tortolina2015 - Multiple signalling pathway associated with colorectal cancer
  • Version: 1 public model Download this version
    • Submitted on: Jan 25, 2016 4:53:26 PM
    • Submitted by: Vijayalakshmi Chelliah
    • With comment: Original import of 22_06_09_ok_APC

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