Epigenetics as a mediator of plasticity in cancer

The concept of an epigenetic landscape describing potential cellular fates arising from pluripotent cells, first advanced by Conrad Waddington, has evolved in light of experiments showing nondeterministic outcomes of regulatory processes and mathematical methods for quantifying stochasticity. In this Review, we discuss modern approaches to epigenetic and gene regulation landscapes and the associated ideas of entropy and attractor states, illustrating how their definitions are both more precise and relevant to understanding cancer etiology and the plasticity of cancerous states. We address the interplay between different types of regulatory landscapes and how their changes underlie cancer progression. We also consider the roles of cellular aging and intrinsic and extrinsic stimuli in modulating cellular states and how landscape alterations can be quantitatively mapped onto phenotypic outcomes and thereby used in therapy development.

Automated summary

This review discusses modern approaches to epigenetic and gene regulation landscapes and their relevance to cancer etiology and the plasticity of cancerous states. The interplay between different types of regulatory landscapes and their changes in cancer progression are addressed. Cellular aging and intrinsic and extrinsic stimuli play important roles in modulating cellular states. Quantitatively mapping landscape alterations onto phenotypic outcomes can be used in therapy development.