Molecular biology and evolution of cancer: from discovery to action

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Abstract

The progression of cancer is an evolutionary process. During this process, evolving populations of cancer cells encounter restrictive ecological niches within the body, such as the primary tumor, the circulatory system, and diverse metastatic sites. Heterogeneous populations of cancer cells undergo selection for adaptive phenotypes, which shapes molecular genetic variation amid concomitant genetic drift. Cell lineages undergo convergent evolution toward phenotypes known as the hallmarks of cancer that promote cancer initiation, growth, and metastasis. Efforts to prevent or delay cancer evolution-and progression-require a deep understanding of the underlying molecular evolutionary processes. Herein we discuss a suite of concepts and tools from evolutionary and ecological theory that can inform-and possibly transform-cancer biology in new and meaningful ways. These concepts and tools include comparative research on cancer across diverse species and application of phylogenetic approaches to analyze the evolution of tumor progression and metastasis. Fitness landscapes can be leveraged to describe potential trajectories of cancer evolution, mapping positive selection and neutral evolution of proto-oncogenes, tumor suppressors, and other functional elements. We also highlight current challenges to applying these concepts and propose research areas that, by incorporating these concepts, could identify new therapeutic modes and vulnerabilities in cancer.