Leading scientists argue for a new paradigm for cancer research, proposing a complex systems view of cancer supported by empirical evidence.Current consensus in cancer research explains cancer as a disease caused by specific mutations in certain genes. After dramatic advances in genome sequencing, never before have we known so much about the individual cancer cell–and yet never before has it been so unclear what to do with this knowledge. In this volume, leading researchers argue for a new theory framework for understanding and treating cancer. The contributors propose a complex systems view of cancer, presenting conceptual building blocks for a new research paradigm supported by empirical evidence.The contributors first discuss the new research framework in terms of theoretical foundations and then take up the relevance of a systems approach, reviewing such topics as nonlinearity, recurrence after treatment, the cellular attractor concept, network theory, and non-coding DNA–the “dark matter” of our genome. They address the temporality of cancer progression, drawing on evolutionary theory and clinical experience. Finally, they cover the dominant role of the tissue microenvironment in cancer, analyzing topics including altered metabolic pathways, the disease-defining influence on metastasis, and the interconnectedness of different environmental niches across levels of organization.