Genetic and Non-Genetic Mechanisms Underlying Cancer Evolution

SIMPLE SUMMARY: Our manuscript summarizes the up-to-date data on the complex and dynamic nature of adaptation mechanisms and evolutionary processes taking place during cancer initiation, development and progression. Although for decades cancer has been viewed as a process governed by genetic mechanisms, it is becoming more and more clear that non-genetic mechanisms may play an equally important role in cancer evolution. In this review, we bring together these fundamental concepts and discuss how those tightly interconnected mechanisms lead to the establishment of highly adaptive quickly evolving cancers. Furthermore, we argue that in depth understanding of cancer progression from the evolutionary perspective may allow the prediction and direction of the evolutionary path of cancer populations towards drug sensitive phenotypes and thus facilitate the development of more effective anti-cancer approaches. ABSTRACT: Cancer development can be defined as a process of cellular and tissular microevolution ultimately leading to malignancy. Strikingly, though this concept has prevailed in the field for more than a century, the precise mechanisms underlying evolutionary processes occurring within tumours remain largely uncharacterized and rather cryptic. Nevertheless, although our current knowledge is fragmentary, data collected to date suggest that most tumours display features compatible with a diverse array of evolutionary paths, suggesting that most of the existing macro-evolutionary models find their avatar in cancer biology. Herein, we discuss an up-to-date view of the fundamental genetic and non-genetic mechanisms underlying tumour evolution with the aim of concurring into an integrated view of the evolutionary forces at play throughout the emergence and progression of the disease and into the acquisition of resistance to diverse therapeutic paradigms. Our ultimate goal is to delve into the intricacies of genetic and non-genetic networks underlying tumour evolution to build a framework where both core concepts are considered non-negligible and equally fundamental.