Benvenuto, F. | Search bioRxiv

bioRxiv2023

In-silico modelling of the mitogen-activated kinase (MAPK) pathway in colorectal cancer: mutations and targeted therapy

Chemical reaction networks are powerful tools for computing the complex nature of cancers onset, progression, and therapy. The main reason for their effectiveness is in the fact that these networks can be rather naturally encoded as a dynamical system whose asymptotic solution mimics the proteins concentration profile at equilibrium. The paper relies on this mathematical approach to investigate global and local effects on the chemical reaction network of the colorectal cancer, triggered by partial and complete mutations occurring in its mitogen-activated kinase (MAPK) pathway. Further, this same approach allowed the in-silico modelling and dosage of a multi-target therapeutic intervention that utilizes MAPK as its molecular target.

systems biology↗

bioRxiv2020

Computational quantification of global effects induced by mutations and drugs in signaling networks of colorectal cancer cells.

Colorectal cancer (CRC) is one of the most deadly and commonly diagnosed tumors worldwide. Several genes are involved in its development and progression. The most frequent mutations concern APC, KRAS, SMAD4, and TP53 genes, suggesting that CRC relies on the alteration of different pathways. However, with classic molecular approaches, it is not easy to simultaneously analyze the interconnections between these pathways. For this reason, we propose a computational model based on a huge chemical reaction network to simulate the effects induced on the global signaling associated with CRC by single or multiple concurrent mutations or by drug treatment. This approach displays several advantages. The model can quantify the alteration in the concentration of the proteins connected with the examined mutation. Moreover, working on the global signaling of CRC, it is possible to disclose unexpected interactions between the involved pathways, representing new therapeutic targets. HighlightsO_LIColorectal cancer relates to defects in many different pathways within cell signaling C_LIO_LICell signaling is modeled as a chemical ration network with 10 interacting pathways C_LIO_LIGlobal effects induced by single or multiple concurrent mutations are quantified C_LIO_LIA possible extension of the model to account for a targeted drug is discussed C_LI

cancer biology↗