Cell-Intrinsic Mechanisms of Drug Tolerance to Systemic Therapies in Cancer

In patients with cancer with metastatic disease, the rate of complete tumor response to systemic therapies is low, and residual lesions persist in the majority of patients due to early molecular adaptation in cancer cells. A growing body of evidence suggests that a subpopulation of drug-tolerant persister cells-a reversible phenotype characterized by reduced drug sensitivity and decreased cell proliferation-maintains residual disease and may serve as a reservoir for resistant phenotypes. The survival of these residual tumor cells can be caused by reactivation of specific signaling pathways, phenotypic plasticity

Automated summary

In patients with metastatic cancer, complete tumor response to systemic therapies is rare due to early molecular adaptation in cancer cells, resulting in residual lesions. Evidence suggests that drug-tolerant persister cells, characterized by reduced drug sensitivity and cell proliferation, play a role in maintaining residual disease and may contribute to resistant phenotypes.