Targeting persister cells: proactively overcoming therapy resistance in aggressive B cell lymphomas

Treatment resistance remains a formidable barrier to curing lymphomas, driven in part by their ability to alter their phenotypic and molecular profiles under therapeutic pressure. A growing body of evidence suggests that a clinically minute population of drug-tolerant persister (DTP) cells, which undergo non-genetic adaptations to survive therapy, are responsible for seeding relapse. We highlight the substantial progress being made to characterize DTP populations, and postulate that they confer novel vulnerabilities for therapeutic targeting. We propose the addition of therapies that proactively address these therapy-induced adaptations to delay or prevent the emergence of resistance in aggressive B cell lymphomas. We contend that this approach can deepen clinical responses, spare patients unnecessary toxicity, and advance progress towards achieving a true cure.