The role of dynamic phenotypes in cancer

Abstract

The question of whether cancer recurrence is mediated by a process that is exclusively Darwinian or that involves both Darwinian and Lamarckian processes is long standing and far from answered. The major open question is the origin of variation, whether it relays exclusively on stable, mostly genetic, mechanisms or whether it can also involve dynamic processes. Recent evidence with single-cell epigenomic and transcriptomic profiling and measurement of phenotypes in colonies indicate that several phenotypes quickly change with a few cell divisions. Most importantly, cell fitness under basal as well as in the presence of chemotherapeutic agents changes considerably over short periods of time and this dynamic is reduced by epigenetic modulators. These studies contribute to establish the dynamic nature of fitness and are key for the interplay between cancer cell dynamics and stable genetic and epigenetic alterations in the survival of a few cancer cells after therapy.