Rethinking Cancer: A New Paradigm for the Postgenomics Era

Description

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. Series Page Title Page Copyright Table of Contents Series Foreword Preface 1. Introduction and Overview I. Redefining the Problem: The Theory Dimension of Cancer 2. The Search for Progress and a New Theory Framework in Cancer Research 3. Cancer as a System: Hard Lessons from Physics and a Way Forward II. The Systems Dimension of Cancer 4. The Logic of Cancer Treatment: Why It Is So Hard to Cure Cancer; Treatment-Induced Progression, Hyper-Progression, and the Nietzsche Effect 5. The Cell Attractor Concept as a Tool to Advance Our Understanding of Cancer 6. Adaptation of Molecular Interaction Networks in Cancer Cells 7. The Role of Genomic Dark Matter in Cancer: Using AI to Shine a Light on It; Why Cancer Genes Are Not the Whole Story III. The Time Dimension of Cancer 8. Darwinism, Not Mutationalism, for New Cancer Therapies 9. Cancer as a Reversion to an Ancestral Phenotype 10. Time and Timing in Oncology: What Therapy Scheduling Can Teach Us about Cancer Biology IV. The Micro-/Environment Dimension of Cancer 11. Tissue Tension Modulates Metabolism and Chromatin Organization to Promote Malignancy 12. Cancer Metabolism and Therapeutic Perspectives: Exploiting Acidic, Nutritional, and Oxidative Stresses 13. Corrupted Vascular Tumor Niches Confer Aggressiveness and Chemoresistance to Neoplastic Cells 14. Metastasis as a Tug of War between Cell Autonomy and Microenvironmental Control: Readdressing Unresolved Questions in Cancer Metastasis 15. Niche Reconstruction to Revert or Transcend the Cancer State V. What Next? Contributors Index