Multicellularity, Phenotypic Heterogeneity, and Cancer

Cancer is a result of the breakdown in processes governing multicellularity, leading to a population of cells that no longer abide by the cues of their multicellular context and begin to act as a population of unicellular organisms within the body. This chapter discusses the interplay between environmental heterogeneity due to positioning of cells within the tumor or within the ecosystem of the body and stochastic heterogeneity that develops without any environmental or genetic differences. Both cellular signals of stress encountered by cancer cells and stochastic gene expression heterogeneity can induce heterogeneous phenotypic responses and differentiation. Synthetic gene circuits can provide new ways to investigate how these heterogeneous phenotypes, driven by both environmental heterogeneity and stochastic gene expression, can be acted upon by natural selection, leading to cancer cell populations with increased fitness.