The Cheating Cell: How Evolution Helps Us Understand and Treat Cancer

In a landmark paper published in 2000, the cancer biologists Douglas Hanahan and Robert Weinberg synthesized decades of investigation in tumor biology to identify six core capabilities acquired by cancer cells during the development and progression of human malignancies. According to their schema, the hallmarks of cancer include sustained proliferation, evading growth suppressors, resisting cell death (apoptosis), enabling replicative immortality, inducing angiogenesis (formation of new blood vessels) and activating invasion and metastasis [1]. Later updated in a follow-up publication to include common tumor characteristics such as abnormal metabolism and the ability to evade the immune system [2], the hallmark papers are now among the most cited in the history of cancer research and have provided a set of organizing principles for both basic and clinical investigators. Athena Aktipis, in her book The Cheating Cell: How Evolution Helps Us Understand and Treat Cancer, urges us to go beyond the hallmarks to understand cancer—and, in so doing, to conceive of new ways to prevent and treat the disease. She makes a compelling case that insights from evolutionary biology and ecology can complement the descriptive phenomenology that has characterized most 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 trillions of cells in our bodies harmoniously cooperate, following what Aktipis calls the multicellularity playbook. Normal cells do not divide uncontrollably, they self-destruct if they become threatening, they share resources, they perform a defined job, and they take care of their local environment. In other words, normal cells do not have any of the hallmarks of cancer, and they occupy a defined niche in a broader ecosystem. Aktipis, a professor at Arizona State University and cofounder of the International Society for Evolution, Ecology and Cancer, sees breakdown of this cellular cooperation as the fundamental characteristic of the cancer cell. The molecular defects that comprise the Hanahan and Weinberg hallmarks of cancer, in this view, are specific mechanisms that cancer cells use to become noncooperators, but defining cancer more broadly as a failure of cooperation provides a comprehensive framework to understand the disease, one that can unify perspectives from tumor genetics, immunology, cell biology and comparative biology. Artfully written in non-technical prose, The Cheating Cell will appeal to both educated lay readers and professionals looking for an introduction to 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 staggering number of cell divisions, and, given the imperfect fidelity of molecular editing, 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. It simply takes time to develop the requisite number of mutations, in the right combination, for cancer to develop. Subsequent chapters lay out the argument for viewing cancer through an evolutionary lens. Aktipis first notes that a population of cancer cells