Dataset Information

Advances in dynamic modeling of colorectal cancer signaling-network regions, a path toward targeted therapies.

ABSTRACT: The interconnected network of pathways downstream of the TGF?, 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: Tortolina L

PROVIDER: S-EPMC4467132 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Advances in dynamic modeling of colorectal cancer signaling-network regions, a path toward targeted therapies.

Tortolina Lorenzo L Duffy David J DJ Maffei Massimo M Castagnino Nicoletta N Carmody Aimée M AM Kolch Walter W Kholodenko Boris N BN De Ambrosi Cristina C Barla Annalisa A Biganzoli Elia M EM Nencioni Alessio A Patrone Franco F Ballestrero Alberto A Zoppoli Gabriele G Verri Alessandro A Parodi Silvio S

Oncotarget 20150301 7

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 ...[more]

PMID: 25671297

Similar Datasets

Project description:Acute myeloid leukemia (AML) is the most common acute leukemia in adults. While survival for younger patients over the last several decades has improved nearly sixfold with the optimization of intensive induction chemotherapy and allogeneic stem cell transplantation (alloHSCT), this effect has been largely mitigated in older and less fit patients as well as those with adverse-risk disease characteristics. However, the last 10 years has been marked by major advances in the molecular profiling of AML characterized by a deeper understanding of disease pathobiology and therapeutic vulnerabilities. In this regard, the classification of AML subtypes has recently evolved from a morphologic to a molecular and genetic basis, reflected by recent updates from the World Health Organization and the new International Consensus Classification system. After years of stagnation in new drug approvals for AML, there has been a rapid expansion of the armamentarium against this disease since 2017. Low-intensity induction therapy with hypomethylating agents and venetoclax has substantially improved outcomes, including in those previously considered to have a poor prognosis. Furthermore, targeted oral therapies against driver mutations in AML have been added to the repertoire. But with an accelerated increase in treatment options, several questions arise such as how to best sequence therapy, how to combine therapies, and if there is a role for maintenance therapy in those who achieve remission and cannot undergo alloHSCT. Moreover, certain subtypes of AML, such as those with TP53 mutations, still have dismal outcomes despite these recent advances, underscoring an ongoing unmet need and opportunity for translational advances. In this review, we will discuss recent updates in the classification and risk stratification of AML, explore the literature regarding low-intensity and novel oral combination therapies, and briefly highlight investigative agents currently in early clinical development for high-risk disease subtypes.

Dataset Information

Advances in dynamic modeling of colorectal cancer signaling-network regions, a path toward targeted therapies.

Publications

Advances in dynamic modeling of colorectal cancer signaling-network regions, a path toward targeted therapies.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets