Precis This book is a treatise about the origin of cancers. I would like to convince readers that the basic tenets of the theory of a stem-cell origin of cancers also constitute a unified theory of cancer. Stem-cell origin of normal (and cancer) cells: Vitruvian version Every truth passes through three stages before it is recognized. In the first it is ridiculed, in the second, it is opposed, in the third, it is regarded as self-evident. - Arthur Schopenhauer v vi Preface Every person has a unique story to tell. My story is about cancer. Cancer touches the lives of countless people. Often enough, it leaves indelible tracks. Many lives have been lost; others are forever changed. For those who confront this deadly scourge, there is a sense of urgency, if not of desperation. For those who face im- nent death, life becomes even more precious and carries a special meaning. As an oncologist, I am touched daily by cancer. I feel its inception, evolution, and aft- math. It seems as though we are fighting an incessant war against cancer at the front line in the trenches. This is my story about cancer. Some people are terrific storytellers. Others have incredible tales to tell.

Precis This book is a treatise about the origin of cancers. I would like to convince readers that the basic tenets of the theory of a stem-cell origin of cancers also constitute a unified theory of cancer. Stem-cell origin of normal (and cancer) cells: Vitruvian version Every truth passes through three stages before it is recognized. In the first it is ridiculed, in the second, it is opposed, in the third, it is regarded as self-evident. - Arthur Schopenhauer v vi Preface Every person has a unique story to tell. My story is about cancer. Cancer touches the lives of countless people. Often enough, it leaves indelible tracks. Many lives have been lost; others are forever changed. For those who confront this deadly scourge, there is a sense of urgency, if not of desperation. For those who face im- nent death, life becomes even more precious and carries a special meaning. As an oncologist, I am touched daily by cancer. I feel its inception, evolution, and aft- math. It seems as though we are fighting an incessant war against cancer at the front line in the trenches. This is my story about cancer. Some people are terrific storytellers. Others have incredible tales to tell.

The questions we ask in this book about cancer are actually quite elementary. What is the origin of cancer? Does cancer arise in any cell in the body, or only in certain cells? Is cancer a genetic or a stem-cell disease? We illustrate that cancer is a multicellular rather than a unicellular process, a cellular rather than a genetic problem, and a stem-cell rather than a somatic-cell disease. We reveal that the incredible resemblance between a cancer cell and a stem cell suggests that they are intimately related. The uncanny ingenuity of a cancer cell is also innate in a stem cell. The recognition that cancer has a stem-cell origin indicates that a stem-cell theory of cancer may be the unified theory that we need to make sense of the torrents of new data and new insights into different facets of cancer, to see how they fit together into one picture, and to disarm the disease. A stem-cell theory of cancer can potentially accept, embrace, and integrate all of its genetic, epigenetic, proteomic, and metabolic aspects. Such a unified theory can account for all cancer hallmarks, including metastasis, heterogeneity, dormancy, and immune evasion. It predicts that multimodal therapy may be more beneficial than targeted therapy, and integrated medicine more effective than precision medicine for the management of all but the simplest tumors. It predicts that when we have the correct cancer theory, clinical progress will advance by monumental leaps rather than incremental steps. Indeed, I predict that successful clinical outcomes will ultimately provide irrefutable validation that cancer is a stem-cell disease. Therefore, the thesis of this book is actually quite simple. When we have a pertinent and correct theory of the origin of cancer, all ideas, observations, experiments, and treatments will begin to fall into place and make perfect sense. We would like to convince readers that a stem-cell theory is the elusive, long-sought unified theory, the theory of all theories, of cancer.