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Lineage Tracing Reveals Clone-Specific Responses to Doxorubicin in Triple-Negative Breast Cancer

  • 0Department of Biomedical Engineering, the University of Texas at Austin, Austin, TX, USA.
Biorxiv : the Preprint Server for Biology +

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April 1, 2025

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April 1, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Triple-negative breast cancer treatment reveals clonal diversity changes and distinct subpopulations. Personalized strategies are needed to address tumor heterogeneity and improve outcomes.

Area Of Science

  • Oncology
  • Genomics
  • Molecular Biology

Background

  • Triple-negative breast cancer (TNBC) is aggressive and heterogeneous, posing treatment challenges.
  • Understanding treatment response at a clonal level is crucial for TNBC management.

Purpose Of The Study

  • To investigate the response of TNBC to doxorubicin using a lineage-tracing system.
  • To identify clonal dynamics and transcriptomic changes during doxorubicin treatment in TNBC models.

Main Methods

  • Utilized ClonMapper, a lineage-tracing system combining clonal tags with single-cell RNA-sequencing (scRNA-seq).
  • Analyzed clonal diversity, subpopulation persistence, and phenotypic changes in response to doxorubicin.

Main Results

  • Doxorubicin treatment reduced overall clonal diversity in a dose-dependent manner.
  • No pre-existing resistance signature was identified in surviving clones.
  • Two distinct clonal subpopulations persisted, exhibiting divergent phenotypes and novel expression changes post-treatment.

Conclusions

  • TNBC treatment response is complex, with surviving clones showing diverse phenotypes.
  • Clonal identity does not solely dictate treatment response.
  • Personalized treatment strategies are essential to overcome TNBC heterogeneity.