edited by Bernhard Strauss, Marta Bertolaso, Ingemar Ernberg, and Mina J. Bissell

Series Foreword ix
Preface xi
1 Introduction and Overview 1
I REDEFINING THE PROBLEM: THE THEORY DIMENSION OF CANCER 11
2 The Search for Progress and a New Theory Framework in Cancer Research 13
3 Cancer as a System: Hard Lessons from Physics and a Way Forward 41
II THE SYSTEMS DIMENSION OF CANCER 61
4 The Logic of Cancer Treatment: Why It Is So Hard to Cure Cancer; Treatment-Induced Progression, Hyper-Progression, and the Nietzsche Effect 63
5 The Cell Attractor Concept as a Tool to Advance Our Understanding of Cancer 129
6 Adaptation of Molecular Interaction Networks in Cancer Cells 141
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 163
III THE TIME DIMENSION OF CANCER 185
8 Darwinism, Not Mutationalism, for New Cancer Therapies 187
9 Cancer as a Reversion to an Ancestral Phenotype 205
10 Time and Timing in Oncology: What Therapy Scheduling Can Teach Us about Cancer Biology 227
IV THE MICRO-/ENVIRONMENT DIMENSION OF CANCER 245
11 Tissue Tension Modulates Metabolism and Chromatin Organization to Promote Malignancy 247
12 Cancer Metabolism and Therapeutic Perspectives: Exploiting Acidic, Nutritional, and Oxidative Stresses 271
13 Corrupted Vascular Tumor Niches Confer Aggressiveness and Chemoresistance to Neoplastic Cells 299
14 Metastasis as a Tug of War between Cell Autonomy and Microenvironmental Control: Readdressing Unresolved Questions in Cancer Metastasis 323
15 Niche Reconstruction to Revert or Transcend the Cancer State 353
V WHAT NEXT? 391
Contributors 397
Index 399