Figure 1.

Mechanisms and impact of tumor heterogeneity in clinical bladder cancer progression. (A) Pretreated primary bladder tumors are heterogeneous consisting of lineage defined subpopulations with potential to change in relative proportions during progression or treatment. (B) Bladder cancer cells can acquire transcriptional and phenotype changes (EMT, NE-like) in response to therapeutic stress. (C) Drug tolerant persisters (DTPs) increase in abundance during clinical therapies. This process may be accelerated using drugs at maximum tolerated dosages (MTD). (D) Acquired driver mutations can promote the clonal expansion of cell populations having more aggressive progression kinetics and reduced response to therapies.