Modeling of Cancer Signaling Pathways

MC 5158

Candidate

Remziye Karabekmez, Applied Math, University of Waterloo

Title

Modeling of Cancer Signaling Pathways

Abstract

Cancer is an ongoing problem all over the world. To find a cure to this disease, both clinicians and scientists are looking for a reasonable treatment method. According to Hanahan and Weinberg, one of the hallmarks of cancer is evasion of programmed cell death, referred to as apoptosis. Apoptosis is an important cellular process, and is regulated by many different pathways. Proteins in these pathways contribute to either cell death or cell survival depending on the cell stresses. Much research in systems biology has been devoted to understanding these pathways at the molecular level.

In this study a mathematical model is built to describe apoptosis, and the pathways involving the related proteins p53- and Akt. The primary purpose of the construction of the kinetic model is to verify that this network can exhibit bistability between the pro- and anti-apoptotic proteins. Dynamical network analysis (stability and phase plane portrait analysis) is used to verify bistability. Sensitivity and bifurcation analysis are conducted to determine which parameters have the greatest effect on the system behavior. In future, a complete characterization of the model parameterization will be needed to use this model to address the effects of specific cancer drugs.