Athena Aktipis, in her book The Cheating Cell: How Evolution Helps Us Understand and Treat Cancer, urges us to go beyond the basic hallmarks, to understand cancer; and, in so doing, to think of new ways to prevent and treat the disease.
She makes a compelling case that insights from evolutionary biology and ecology can complement mainstream cancer research.
The core argument of The Cheating Cell is contained in the title of the book: cancer, at the most basic level, can be regarded as ‘the ultimate form of cellular cheating’. Normally, the different types of cells in our bodies cooperate. Normal cells do not divide uncontrollably, they self-destruct (apoptosis) if they become a threat to the organism, they can share resources, they perform a defined job, and they take care of their environment. In other words, normal cells do not have any of the hallmarks of cancer, and they occupy a defined cellular niche in a broader ecosystem.
Aktipis, who is a professor and the founder of the International Society for Evolution, Ecology and Cancer, sees breakdown of this cellular cooperation as the fundamental attribute of cancer cells. The molecular defects are specific mechanisms that cancer cells use to become non-cooperative, but defining cancer more broadly as a failure of cooperation provides a comprehensive framework to understand the disease, that can unify perspectives from tumor genetics, immunology, and cell biology.
Well written in an easy to understand style, The Cheating Cell will appeal to both educated enthusiast readers as well as professionals looking for an introduction to the evolutionary concepts in cancer biology. In the first part of the book, Aktipis identifies cancer as a natural consequence of multicellularity. Over the course of a human lifetime, there are a huge number of cell divisions, and, given the imperfect process of molecular copying, genetic mistakes occur. An accumulation of mutations in so-called driver genes, roughly four to seven, on average, for common tumors such as lung and prostate cancer, eventually produces a fully malignant cell. This is why most cancers increase in incidence with age and cancer is often considered a disease of the aging body. It simply takes time to develop the requisite number of mutations, in the right combination, for cancer to develop, and therefore cancer is inevitable if we were to live long enough to get it.
The subsequent chapters make the argument for viewing cancer through an evolutionary lens. Aktipis first notes that a population of cancer cells meets the basic conditions for evolution through natural selection. They possess genetic variability, their mutations can be inherited, and the traits these variations produce confer selective differences, as a tumor develops and under the selection pressure of treatments such as chemotherapy. These are simple evolutionary concepts, but are too often forgotten in the specialized work of cancer research, but these concepts are central to understanding cancer as a biological process.
Aktipis extends her argument by introducing the notion of evolutionary trade-offs in cancer biology. The cancer cell divides uncontrollably, and fails to undergo programmed cell death and evades the immune system. Each of these features reflects an evolutionary trade-off made by multicellular organisms. Rapid cellular proliferation is essential for us to live, but the same molecular mechanisms that drive proliferation in these settings can be used by the cancer cells. Elimination of genetically damaged cells must be finely balanced. If the mechanisms of suppression are too vigorous, premature aging will occur as normal cells are inappropriately triggered into apoptosis, whereas loss of surveillance and DNA repair mechanisms leads to cancer.
The book finishes its argument in favor of an evolutionary framework by taking the reader through examples of cancers in the animal and even the plant world, such as crested cacti. All of these cases outline and give evidence to the argument that cancer is, at basis, a failure of cellular cooperation.
The book concludes with a discussion of how viewing cancer from an evolutionary perspective can better guide our approach to treatment and the development of new drugs. Aktipis spends a number of pages describing adaptive therapy, an approach that aims to vary the doses and combinations of drugs over time to control, but not eradicate, a tumor, much as farmers employ pest management strategies that use lower doses of pesticides to maintain pest infestations at an acceptable level. Adaptive therapy in various forms has been tried in a number of tumors, but it is not yet clear if it provides an advantage over the standard approaches.
In the last few decades the development of targeted therapies and immunotherapy has transformed the treatment of many cancers, and there is now enormous opportunity in combining what we have learned at a molecular level about the response and resistance of tumors to these new treatments with the framework presented in this book.
Perhaps a combination of all of our cancer knowledge could lead us to developing a combination approach to finally bring cancer under medical control.
This book is a fascinating read and can be especially recommend to university students who wish to pursue a career in the related fields.