Abstract
New applications of evolutionary biology are transforming our understanding of cancer. The articles in this special issue provide many specific examples, such as microorganisms inducing cancers, the significance of within-tumor heterogeneity, and the possibility that lower dose chemotherapy may sometimes promote longer survival. Underlying these specific advances is a large-scale transformation, as cancer research incorporates evolutionary methods into its toolkit, and asks new evolutionary questions about why we are vulnerable to cancer. Evolution explains why cancer exists at all, how neoplasms grow, why cancer is remarkably rare, and why it occurs despite powerful cancer suppression mechanisms. Cancer exists because of somatic selection; mutations in somatic cells result in some dividing faster than others, in some cases generating neoplasms. Neoplasms grow, or do not, in complex cellular ecosystems. Cancer is relatively rare because of natural selection; our genomes were derived disproportionally from individuals with effective mechanisms for suppressing cancer. Cancer occurs nonetheless for the same six evolutionary reasons that explain why we remain vulnerable to other diseases. These four principles—cancers evolve by somatic selection, neoplasms grow in complex ecosystems, natural selection has shaped powerful cancer defenses, and the limitations of those defenses have evolutionary explanations—provide a foundation for understanding, preventing, and treating cancer.
Conclusion
The benefits of using evolutionary principles to understand cancer provide a specific example of the benefits of evolutionary medicine more generally. An evolutionary approach can help us understand why cancer exists and how it progresses (somatic evolution), how cancer cells interact with environments (ecological approaches), why it is not more common (natural selection for cancer suppression mechanisms), and why cancer suppression mechanisms can never be perfect (constraints, trade-offs, and other evolutionary reasons for vulnerability to disease). Evolution is essential for understanding cancer. It provides a framework for studying the evolutionary origins and progression of cancer that is parallel and complementary to the Hallmarks of Cancer framework for studying the mechanisms of cancer.
The importance of an evolutionary understanding cancer is not just an academic pursuit; it has great clinical utility that remains largely untapped. Evolutionary theory and methods have led to critical advances that promise to improve how we understand and treat cancer. For example, the finding that diversity in the premalignant biopsies predicts progression to cancer (Maley et al. 2006; Merlo et al. 2010) suggests methods for risk stratification, and a focus of clinical resources on those patients with the highest likelihood of cancer progression. Also, the development of novel therapeutic approaches, such as Gatenby's adaptive therapy algorithm (Gatenby et al. 2009), holds the promise of revolutionizing the way some cancers are treated—shifting the focus from eliminating every cancer cell, to controlling cancer by manipulating selection forces within the tumor. An evolutionary analysis of chemotherapy resistance suggests that taking another biopsy after a relapse may identify resistant mutations and guide targeted second line therapies. Finally, a clearer understanding of how large organisms suppress cancer (Caulin and Maley 2011), and the trade-offs inherent in cancer suppression, will inspire new strategies for risk assessment and cancer prevention. An example is provided by Hochberg et al.'s (this issue) discussion of new strategies to limit or eradicate incipient neoplasms by reducing microinflammation which may spur neoplastic progression, and by reducing the accumulation of DNA damage by administering poly ADP ribose polymerase inhibitors.
In retrospect, it is remarkable that the evolution of cells within tumors was not recognized until the 1970s with Nowell's (1976) paper ‘The clonal evolution of tumor cell populations.’ Despite subsequent wide acceptance of evolutionary explanations for cancer progression, applications of evolutionary thinking remain limited; for instance, evolutionary terms are used in only about 1% of the abstracts of papers on therapeutic resistance (Aktipis et al. 2011). While applications of evolutionary principles to the problems of cancer are in their infancy, they are growing fast, as illustrated by many recent conferences across the world, and the creation of two centers for the study of evolution and cancer, the Center for Evolution and Cancer at the University of California, San Francisco, and the Centre for Ecological and Evolutionary Cancer Research at University of Montpellier. We anticipate that evolutionary applications that advance cancer research and treatment will speed the growth of evolutionary medicine more generally, and that as more physicians have opportunities to learn the basic science of evolutionary biology, their insights will further advance our understanding of cancer, as well as the rest of medicine.
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