Using Systems Biology to Understand Cancer as an Evolutionary Process

Unsatisfactory progress in cancer medicine and prevention calls for new research approaches. Research can broaden its view of cancer to include not only specific molecular elements, but also the process that explains their origin and dynamics. This process is Darwinian evolution of somatic cells. Applicable modeling techniques are available from process-oriented systems biology. We review relevant concepts and techniques, and their application to four key open questions in cancer prevention research. Helpful concepts are transferable from classical evolutionary biology and ecology, while useful techniques include computational agent-based modeling. The research questions we review include (1) why do benign neoplasms often progress to malignancy? (2) what is the chronological sequence of molecular events in cancer progression? (3) how can we find reliable molecular biomarkers for cancer? and (4) will evolved drug resistance stymie efforts at a long-term cancer chemoprevention? We conclude that molecular analysis can be usefully augmented with process-oriented systems biology to guide empirical research into the most productive directions.