Cancer systems biology: From molecular profiles to pathways, signalling networks, and therapeutic vulnerabilities

Cancer systems biology encompasses the application of systems biology approaches to cancer research. Historically, systems biology was first applied in cancer research to enable a pathway-oriented interpretation of gene expression data and this strategy has undoubtedly delivered relevant insights with respect to many aspects of cancer biology. Nowadays, cancer is regarded as a complex system that integrates signals from different levels (i.e. (epi)genomics, transcriptomics, micro-environment) through a network of interconnected proteins to generate a biological response. This holistic approach not only allows the identification of new and relevant signal transduction pathways, but also provides a better understanding of several key properties of cancer cells that can be best understood from a network-level perspective: robustness, evolvability, and plasticity. This chapter provides an overview of several key concepts of systems biology, including reference gene set libraries, network topology, and available strategies to establish biological networks. Next, these concepts are utilized to explain gene set and gene network analysis with particular focus on cancer biology. Finally, the caveats and challenges that are facing cancer systems biology are summarized.