Molecular Biology and Evolution of Cancer: From Discovery to Action.

Cancer progression is an evolutionary process. During this process, evolving cancer cell populations encounter restrictive ecological niches within the body, such as the primary tumor, circulatory system, and diverse metastatic sites. 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 cancer biology in new and meaningful ways. We also highlight current challenges to applying these concepts, and propose ways in which incorporating these concepts could identify new therapeutic modes and vulnerabilities in cancer.

Niche explosion.

The following syndrome of features occurs in several groups of phytophagous insects: (1) wingless females, (2) dispersal by larvae, (3) woody hosts, (4) extreme polyphagy, (5) high abundance, resulting in status as economic pests, (6) invasiveness, and (7) obligate parthenogenesis in some populations. If extreme polyphagy is defined as feeding on 20 or more families of hostplants, this syndrome is found convergently in several species of bagworm moths, tussock moths, root weevils, and 5 families of scale insects. We hypothesize that extreme polyphagy in these taxa results from "niche explosion", a positive feedback loop connecting large population size to broad host range. The niche explosion has a demographic component (sometimes called the "amplification effect" in studies of pathogens) as well as a population-genetic component, due mainly to the increased effectiveness of natural selection in larger populations. The frequent origins of parthenogenesis in extreme polyphages are, in our interpretation, a consequence of this increased effectiveness of natural selection and consequent reduced importance of sexuality. The niche explosion hypothesis makes detailed predictions about the comparative genomics and population genetics of extreme polyphages and related specialists. It has a number of potentially important implications, including an explanation for the lack of observed trade-offs between generalists and specialists, a re-interpretation of the ecological correlates of parthenogenesis, and a general expectation that Malthusian population explosions may be amplified by Darwinian effects.