Fig. 1

Changes in acquired therapy resistance induced by treatment initiation and discontinuation, with different scenarios employed to interpret the development of the therapy-resistant phenotype. According to the Darwinian selection model, drug-tolerant persistors (DTPs) that originated from the primary tumor tissue are selected and enriched by treatments. The Lamarckian induction model regards the acquired drug-indifferent phenotype as the result of tumor cell adaptation to treatments that leads to formation of induced DTPs. The coexisting model suggests that formation of both primary and induced DTPs occur and together contribute to the acquired therapy resistance