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Steroid hormone receptors, exome sequencing and treatment responsiveness of breast cancer patient-derived xenografts originated in a South American country

  • 0Laboratory of Hormonal Carcinogenesis, IBYME-CONICET, Ciudad Autónoma de Buenos Aires (CABA), V. Obligado 2490, C1428ADN, Buenos Aires, Argentina.
Scientific Reports +

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January 18, 2025

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January 18, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

This study developed the first breast cancer patient-derived xenografts from South American patients, crucial for precision medicine. These models, expressing androgen and glucocorticoid receptors, show promise for testing novel endocrine therapies, even in triple-negative breast cancer.

Area Of Science

  • Oncology
  • Genetics
  • Pharmacology

Background

  • Patient-derived xenografts (PDX) are vital for precision medicine in breast cancer (BC).
  • A gap exists in PDX models from South American BC patients, despite ethnic influences on outcomes.
  • Developing diverse PDX models is essential for comprehensive research.

Purpose Of The Study

  • To establish and characterize BC PDX models from South American patients.
  • To analyze receptor expression (ER, PR, AR, GR), cytokeratins, EGFR, and HER2.
  • To identify mutations and evaluate in vivo/ex vivo drug responses for precision medicine.

Main Methods

  • Surgical BC fragments were used to create PDX in NSG mice.
  • Immunohistochemistry, molecular studies, and whole exome sequencing were performed.
  • In vivo and ex vivo drug sensitivity assays were conducted.

Main Results

  • Eight PDX models were successfully established, including ER+, HER2+, and triple-negative (TN) subtypes.
  • Receptor expression (ER, PR, AR, GR) varied, with AR/GR co-expression noted in ER+ and some TN tumors.
  • Specific PDX showed sensitivity to targeted therapies (e.g., palbociclib, trastuzumab, alpelisib) and conventional chemotherapies.

Conclusions

  • The study reports the first genetically and biologically characterized BC PDX from South American populations.
  • These novel PDX models are valuable resources for precision medicine research.
  • PDX models expressing AR and/or GR can aid in evaluating endocrine therapies for various BC subtypes, including TNBC.

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