Catastrophic shifts and lethal thresholds in a propagating front model of unstable tumour progression

Abstract

Unstable dynamics characterizes the evolution of most solid tumors. Because of an increased failure of maintaining genome integrity, a cumulative increase in the levels of gene mutation and loss is observed. Previous work suggests that instability thresholds to cancer progression exist, defining phase transition phenomena separating tumor-winning scenarios from tumor extinction or coexistence phases. Here we present an integral equation approach to the quasispecies dynamics of unstable cancer. The model exhibits two main phases, characterized by either the success or failure of cancer tissue. Moreover, the model predicts that tumor failure can be due to either a reduced selective advantage over healthy cells or excessive instability. We also derive an approximate, analytical solution that predicts the front speed of aggressive tumor populations on the instability space.