Hypothesis: Cancer Is a Disease of Evolved Trade-Offs Between Neoplastic Virulence and Transmission.

Virulence is defined as the ability of a pathogen to cause morbidity and/or mortality in infected hosts. The relationship between virulence and transmissibility is complex; natural selection may promote decreased virulence to enhance host mobility and increase the probability for transmission, or transmissibility may be enhanced by increased virulence, leading to higher pathogen load and, in some cases, superior evasion from host defenses. An evolutionary trade-off exists between the ability of pathogens to maintain opportunities for long-term transmission via suppressed virulence and increased short-term transmission via enhanced virulence. We propose an analogy between transmissibility and virulence in microbial pathogens and in cancer. Thus, in the latter case, the outcome of invasive growth and metastasis is analogous to transmissibility, and virulence is defined by high rates of proliferation, invasiveness and motility, potential for metastasis, and the extent to which the cancer contributes to patient morbidity and mortality. Horizontal and vertical transmission, associated with increased or decreased pathogen virulence respectively, can also be utilized to model the neoplastic process and factors that would increase or decrease tumor aggressiveness. Concepts of soft vs. hard selection and evolutionary game theory can optimize our understanding of carcinogenesis and therapeutic strategies. Therefore, the language of transmissibility, horizontal vs. vertical transmission, selection, and virulence can be used to inform approaches to inhibit tumorigenic progression, and, more generally, for cancer prevention and treatment.