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  11. An Optimised Patient-derived Explant Platform For Breast Cancer Reflects Clinical Responses To Chemotherapy And Antibody-directed Therapy

An optimised patient-derived explant platform for breast cancer reflects clinical responses to chemotherapy and antibody-directed therapy

Constantinos Demetriou1, Naila Abid1, Michael Butterworth1

  • 1Leicester Cancer Research Centre, University of Leicester, Clinical Sciences Building, Leicester, LE2 7LX, UK.

Scientific Reports
|June 4, 2024

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View abstract on PubMed

Summary
This summary is machine-generated.

Patient-derived explants (PDEs) offer a novel preclinical platform for breast cancer research. This approach accurately predicts patient response to chemotherapy and HER2-targeted therapies, improving treatment strategies.

Area of Science:

  • Oncology
  • Pathology
  • Biomedical Engineering

Background:

  • Breast cancer is a leading global cancer in women, with many tumors resistant to current treatments.
  • Novel preclinical models are crucial for developing more effective breast cancer therapies.

Purpose of the Study:

  • To evaluate patient-derived explants (PDEs) as a preclinical platform for breast cancer research.
  • To investigate biomarker changes in tumor and stromal areas using digital pathology and multi-immunofluorescence.
  • To assess the correlation between PDE responses and patient clinical outcomes.

Main Methods:

  • Short-term culture of intact breast cancer fragments as patient-derived explants (PDEs).
  • Inclusion of autologous serum to maintain tumor architecture and immune microenvironment.
Keywords:
Breast cancerHER2Multi-immunofluorescencePatient-derived explants

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  • Application of digital pathology and multi-immunofluorescence for biomarker analysis.
  • Correlation of cell death/proliferation responses to chemotherapy (FET) and antibody therapy (trastuzumab) with patient progression-free survival and HER2 status.

    • Main Results:

    • Breast cancer PDEs retained intact immune microenvironments and tumor architecture.
    • Cell death and proliferation responses in PDEs to FET chemotherapy significantly correlated with patient progression-free survival.
    • Cell death responses to trastuzumab therapy in PDEs correlated significantly with HER2 status.

    Conclusions:

    • The PDE platform, coupled with digital pathology, serves as a robust preclinical model for predicting clinical responses to chemotherapy and antibody-based therapies in breast cancer.
    • PDEs facilitate the preclinical testing of novel anti-cancer agents targeting the tumor microenvironment due to their preserved architecture.
    Therapies