Systems Biology Analysis of Cell Death Pathways in Cancer: How Collaborative and Interdisciplinary Research Helps

Abstract

Programmed cell death, together with proliferation and differentiation, is responsible for maintaining the population of cells in all tissues. Dysregulation in this genetically-regulated process plays an important role in the pathophysiology of different disorders. Excessive cell death is pathogenic when it concerns post-mitotic cells and results in various diseases, such as infarction, stroke or neurodegenerative disorders. Insufficient cell death also results in a series of diseases, among which is cancer. Since cancer cells are so different, these cells can be used as an example (model) of how one can understand the whole system qualitatively and quantitatively. In this chapter the various cell death pathways are described. These pathways are central to cancer progression and to the understanding and optimal treatment of individual cancers. The complexity and interweaving of these pathways and the various feedback mechanisms indicate that a systems biology approach with mathematical modelling is needed to fully describe and understand the processes involved. The models based on these studies are crucial to effective drug development, drug testing, and optimal choice of combination therapies, since extensive molecular data for each type of cancer, personalized to each patient’s history and genetic makeup, can be analysed. In addition, we focus on the question of why highly interdisciplinary approaches are required, and why common data, languages, and approaches are needed for optimum data analysis and clinical applications. This can often be effectively accomplished with multiple laboratory collaboration. An example of these collaborative efforts is given by the European Commission funded programs. Collaborative research helps to achieve the main goal of developing new approaches to rational strategies for cancer treatment.