Drug-Tolerant Persister (DTP) Cells

Drug-tolerant persister (DTP) cells are a reversible, non-genetically-encoded state that cancer cells can enter during targeted therapy or chemotherapy, allowing them to survive treatment without acquiring resistance-conferring mutations. DTP cells remodel their lipid metabolism and become selectively dependent on the ferroptosis-suppressing enzyme GPX4, a vulnerability that does not exist in the original, drug-sensitive tumor cells. Because this persister state is thought to precede — and is reversible before — the emergence of fully resistant clones, therapeutically timed ferroptosis induction has been proposed as a strategy to eliminate persister cells during minimal residual disease, before relapse-driving resistance mutations can arise.