An agent-based modeling framework linking inflammation and cancer using evolutionary principles: description of a generative hierarchy for the hallmarks of cancer and developing a bridge between mechanism and epidemiological data

Mathematical Biosciences
Gary An, Swati Kulkarni

Abstract

Inflammation plays a critical role in the development and progression of cancer, evident in multiple patient populations manifesting increased, non-resolving inflammation, such as inflammatory bowel disease, viral hepatitis and obesity. Given the complexity of both the inflammatory response and the process of oncogenesis, we utilize principles from the field of Translational Systems Biology to bridge the gap between basic mechanistic knowledge and clinical/epidemiologic data by integrating inflammation and oncogenesis within an agent-based model, the Inflammation and Cancer Agent-based Model (ICABM). The ICABM utilizes two previously published and clinically/epidemiologically validated mechanistic models to demonstrate the role of an increased inflammatory milieu on oncogenesis. Development of the ICABM required the creation of a generative hierarchy of the basic hallmarks of cancer to provide a foundation to ground the plethora of molecular and pathway components currently being studied. The ordering schema emphasizes the essential role of a fitness/selection frame shift to sub-organismal evolution as a basic property of cancer, where the generation of genetic instability as a negative effect for multicellular eukaryotic organ...Continue Reading

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