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.

Series Foreword ixPreface xi1 Introduction and Overview 1I REDEFINING THE PROBLEM: THE THEORY DIMENSION OF CANCER 112 The Search for Progress and a New Theory Framework in Cancer Research 133 Cancer as a System: Hard Lessons from Physics and a Way Forward 41II THE SYSTEMS DIMENSION OF CANCER 614 The Logic of Cancer Treatment: Why It Is So Hard to Cure Cancer; Treatment-Induced Progression, Hyper-Progression, and the Nietzsche Effect 635 The Cell Attractor Concept as a Tool to Advance Our Understanding of Cancer 1296 Adaptation of Molecular Interaction Networks in Cancer Cells 1417 The Role of Genomic Dark Matter in Cancer: Using AI to Shine a Light on It; Why Cancer Genes Are Not the Whole Story 163III THE TIME DIMENSION OF CANCER 1858 Darwinism, Not Mutationalism, for New Cancer Therapies 1879 Cancer as a Reversion to an Ancestral Phenotype 20510 Time and Timing in Oncology: What Therapy Scheduling Can Teach Us about Cancer Biology 227IV THE MICRO-/ENVIRONMENT DIMENSION OF CANCER 24511 Tissue Tension Modulates Metabolism and Chromatin Organization to Promote Malignancy 24712 Cancer Metabolism and Therapeutic Perspectives: Exploiting Acidic, Nutritional, and Oxidative Stresses 27113 Corrupted Vascular Tumor Niches Confer Aggressiveness and Chemoresistance to Neoplastic Cells 29914 Metastasis as a Tug of War between Cell Autonomy and Microenvironmental Control: Readdressing Unresolved Questions in Cancer Metastasis 32315 Niche Reconstruction to Revert or Transcend the Cancer State 353V WHAT NEXT? 391Contributors 397Index 399