Paper detail

From gene regulatory networks to population dynamics: robustness, diversity and their role in progression to cancer

The aim of this paper is to discuss the role of robustness and diversity in population dynamics in particular to some properties of the multi-step from healthy tissue to fully malignant tumours. Recent evidence shows that diversity within the cell population of a neoplasm, a pre-tumoural lession that can develop into a fully malignant tumour, is the best predictor for its evolving into a tumour. By studying the dynamics of a population described by a multi-type, population-size limited branching process in terms of the evolutionary formalism, we show some general principles regarding the probability of a resident population to being invaded by a mutant population in terms of the number of types present in the population and their resilience. We show that, although diversity in the mutant population poses a barrier for the emergence of the initial (benign) lession, under appropiate conditions, namely, the phenotypes in the mutant population being more resilient than those of the resident population, a more variable noeplastic population is more likely to be invaded by a more malignant one. Analysis of a model of gene regulatory networks suggest possible mechanisms giving rise to mutants with increased phenotypic diversity and robustness. We then go on to show how these results may help us to interpret some recent data regarding the evolution of Barrett's oesophagus into throat cancer.