Landscaping the epigenetic landscape of cancer

摘要

Waddington's epigenetic landscape was introduced in biology for understanding the complex process of metazoan development in an accessible fashion. The epigenetic landscape concept implies the coupling of cell differentiation and tissue/organ morphogenesis under a simple visual metaphor or analogy with significant heuristic value. Yet in recent times the epigenetic landscape has been reduced to an illustration device just for cell differentiation thus diminishing its explanatory power and heuristic value. On the other hand, the current mainstream in cancer research is concentrated on the search for proximate causes but not on achieving a deeper understanding of the phenomenon. Nevertheless an emerging alternative perspective that understands cancer as a problem related to tissue/organ morphology and structural organization is getting wider attention. Within such a perspective here we present and discuss a historically restored, non-reductionist, version of the epigenetic landscape that when applied to the problem of cancer improves our understanding of it as a common biological phenomenon resulting from the uncoupling of morphogenesis and cell differentiation as a consequence of the progressive erosion of the epigenetic landscape. The following discussion aims at finding a general framework, not dependent on proximate causes, for understanding the phenomenon of cancer and suggests new research strategies on this problem but away from the current emphasis on the putative genetic causes of cancer. (C) 2018 Elsevier Ltd. All rights reserved.