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Single-cell Transcriptomic Analyses of Mouse Pancreatic Endocrine Cells
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Single-cell transcriptomics reveals multi-step adaptations to endocrine therapy.

Sung Pil Hong1,2, Thalia E Chan3, Ylenia Lombardo4,5

  • 1Department of Surgery and Cancer, Imperial College London, London, UK. s.hong@imperial.ac.uk.

Nature Communications
|September 4, 2019
PubMed
Summary
This summary is machine-generated.

Endocrine therapy resistance in breast cancer involves more than just genetic changes. A rare subpopulation of pre-adapted cells drives resistance through genetic and transcriptional reprogramming, suggesting new biomarker strategies.

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Area of Science:

  • Oncology
  • Genetics
  • Cell Biology

Background:

  • Endocrine therapy (ET) resistance in luminal breast cancer is complex, involving more than Darwinian selection.
  • Late relapses suggest a interplay between genetic and non-genetic factors in treatment resistance.

Purpose of the Study:

  • To dissect the roles of genetic diversity and transcriptional plasticity in ET resistance at single-cell resolution.
  • To define mechanisms driving early and late-phase resistance to endocrine therapy.

Main Methods:

  • Single-cell RNA-sequencing and imaging were employed to analyze cell populations.
  • Transcriptional variability and copy number changes were assessed in detail.

Main Results:

  • A rare subpopulation of pre-adapted (PA) cells was identified, capable of transcriptomic reprogramming and copy number alterations.
  • Evidence of PA signature expression was found in primary tumors and circulating tumor cells.
  • A multi-step model for ET resistance development was proposed.

Conclusions:

  • Breast cancer endocrine therapy resistance is a multi-step process involving genetic and non-genetic factors.
  • Pre-adapted cells play a critical role in the development of full resistance.
  • Stage-specific biomarkers are recommended for improved treatment monitoring and intervention.