Cellular and molecular mechanisms of plasticity in cancer

Cancer cells are plastic - they can assume a wide range of distinct phenotypes. Plasticity is integral to cancer initiation and progression, as well as to the emer-gence and maintenance of intratumoral heterogeneity. Furthermore, plastic cells can rapidly adapt to and evade therapy, which poses a challenge for effec-tive cancer treatment. As such, targeting plasticity in cancer holds tremendous promise. Yet, the principles governing plasticity in cancer cells remain poorly understood. Here, we provide an overview of the fundamental molecular and cellular mechanisms that underlie plasticity in cancer and in other biological contexts, including development and regeneration. We propose a key role for high-plasticity cell states (HPCSs) as crucial nodes for cell state transitions and enablers of intra-tumoral heterogeneity.