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

Jianguo Tao1, Kevin Qiu1, Michael E Williams2

  • 1Department of Pathology, University of Virginia Comprehensive Cancer Center, Charlottesville, VA 22908, USA.

Trends in Cancer
|January 8, 2026
PubMed

Insights

Drug-tolerant persister (DTP) cells in lymphomas adapt to survive therapy, driving treatment resistance and relapse. Targeting these non-genetically adapting cells offers new strategies to improve lymphoma cures.

Area of Science:

  • Oncology
  • Hematology
  • Cancer Biology

Background:

  • Treatment resistance is a major obstacle in curing lymphomas.
  • Lymphomas can change their molecular and phenotypic profiles under therapy.
  • Drug-tolerant persister (DTP) cells are a small cell population that survives therapy through non-genetic adaptations.

Purpose of the Study:

  • To highlight progress in characterizing DTP populations in lymphomas.
  • To propose targeting DTP cells and their adaptive mechanisms.
  • To suggest strategies for preventing or delaying therapeutic resistance.

Main Methods:

  • Review of current research on DTP cell characterization.
  • Analysis of DTP cell-mediated drug resistance mechanisms.
  • Postulation of therapeutic strategies targeting DTP vulnerabilities.

Main Results:

  • DTP cells are implicated in seeding lymphoma relapse after therapy.
  • DTP cells exhibit unique adaptive mechanisms conferring drug tolerance.
  • Characterization of DTP populations reveals potential therapeutic vulnerabilities.

Conclusions:

  • Targeting DTP cells and their adaptive strategies is a promising approach to overcome lymphoma treatment resistance.
  • Proactive therapeutic strategies addressing therapy-induced adaptations can prevent resistance emergence in aggressive B cell lymphomas.
  • This approach may deepen clinical responses, reduce toxicity, and advance lymphoma cure rates.
Keywords:
B cell lymphomadrug-tolerant persister cellsimmunotherapytargeted therapytherapy-induced resistance

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