Figure 2. Towards a phenomenological and mechanistic understanding of the dynamics of drug tolerant phenotypic states.
(A) The reconstitution of phenotypic diversity after clonal expansion can provide insights into the stability of drug tolerant states.
(B) Live-cell imaging provides the opportunity to zoom into the process of diversity generation from a single cell. By combining information about lineage relationships and end-point single cell phenotype, it is possible to estimate the rates of phenotypic transitions. Adapted from Hormoz et al. [30].
(C) Understanding the way fluctuations in signaling molecules interact with stabilization mechanisms, such as self-reinforcing feedback loops and epigenetic modifications, is critical for controlling the emergence of drug-tolerant states before and after treatment.