Cell Cycling Models of Carcinogenesis: A Complex Systems Analysis

TL;DR

This paper presents a complex systems approach to modeling cell cycling in carcinogenesis, emphasizing the role of cyclins and proposing new therapeutic strategies based on signaling pathways.

Contribution

It introduces a novel theoretical framework analyzing nonlinear dynamics of cell cycle networks involved in cancer development.

Findings

Highlights the importance of cyclins D1 and E in cancer progression

Suggests new clinical trials targeting cell cycle regulation

Proposes therapies to restore cell cycle inhibition in metastatic cancer

Abstract

A new approach to the modular, complex systems analysis of nonlinear dynamics in cell cycling network transformations involved in carcinogenesis is proposed. Carcinogenesis is a complex process that involves dynamically inter-connected biomolecules in the intercellular, membrane, cytosolic, nuclear and nucleolar compartments that form numerous inter-related pathways. One such family of pathways contains the cell cyclins. Cyclins are proteins that link several critical pro-apoptotic and other cell cycling/division components, including the tumor suppressor gene TP53 and its product, the Thomsen-Friedenreich antigen (T antigen), Rb, mdm2, c-Myc, p21, p27, Bax, Bad and Bcl-2, which all play major roles in neoplastic transformation of many tissues. This novel theoretical analysis based on recently published studies of cyclin signaling, with special emphasis placed on the roles of cyclins D1 and E, suggests novel clinical trials and rational therapies of cancer through reestablishment of cell cycling inhibition in metastatic cancer cells.