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Landscapes of cellular phenotypic diversity in breast cancer xenografts and their impact on drug response

Author

Listed:
  • Dimitra Georgopoulou

    (University of Cambridge)

  • Maurizio Callari

    (University of Cambridge)

  • Oscar M. Rueda

    (University of Cambridge)

  • Abigail Shea

    (University of Cambridge)

  • Alistair Martin

    (University of Cambridge)

  • Agnese Giovannetti

    (University of Cambridge
    Laboratory of Clinical Genomics, Fondazione IRCCS Casa Sollievo della Sofferenza)

  • Fatime Qosaj

    (University of Cambridge)

  • Ali Dariush

    (University of Cambridge
    University of Cambridge)

  • Suet-Feung Chin

    (University of Cambridge)

  • Larissa S. Carnevalli

    (Bioscience, Oncology, Early Oncology R&D, AstraZeneca)

  • Elena Provenzano

    (Breast Cancer Programme, CRUK Cambridge Centre
    Cambridge University Hospitals NHS Foundation Trust)

  • Wendy Greenwood

    (University of Cambridge)

  • Giulia Lerda

    (University of Cambridge)

  • Elham Esmaeilishirazifard

    (University of Cambridge
    Bioscience, Oncology, Early Oncology R&D, AstraZeneca)

  • Martin O’Reilly

    (University of Cambridge)

  • Violeta Serra

    (Experimental Therapeutics Group, Vall d’Hebron Institut d’Oncologia)

  • Dario Bressan

    (University of Cambridge)

  • Gordon B. Mills

    (Oregon Health & Sciences University)

  • H. Raza Ali

    (University of Cambridge)

  • Sabina S. Cosulich

    (Bioscience, Oncology, Early Oncology R&D, AstraZeneca)

  • Gregory J. Hannon

    (University of Cambridge)

  • Alejandra Bruna

    (University of Cambridge)

  • Carlos Caldas

    (University of Cambridge
    Breast Cancer Programme, CRUK Cambridge Centre
    Cambridge University Hospitals NHS Foundation Trust)

Abstract

The heterogeneity of breast cancer plays a major role in drug response and resistance and has been extensively characterized at the genomic level. Here, a single-cell breast cancer mass cytometry (BCMC) panel is optimized to identify cell phenotypes and their oncogenic signalling states in a biobank of patient-derived tumour xenograft (PDTX) models representing the diversity of human breast cancer. The BCMC panel identifies 13 cellular phenotypes (11 human and 2 murine), associated with both breast cancer subtypes and specific genomic features. Pre-treatment cellular phenotypic composition is a determinant of response to anticancer therapies. Single-cell profiling also reveals drug-induced cellular phenotypic dynamics, unravelling previously unnoticed intra-tumour response diversity. The comprehensive view of the landscapes of cellular phenotypic heterogeneity in PDTXs uncovered by the BCMC panel, which is mirrored in primary human tumours, has profound implications for understanding and predicting therapy response and resistance.

Suggested Citation

  • Dimitra Georgopoulou & Maurizio Callari & Oscar M. Rueda & Abigail Shea & Alistair Martin & Agnese Giovannetti & Fatime Qosaj & Ali Dariush & Suet-Feung Chin & Larissa S. Carnevalli & Elena Provenzano, 2021. "Landscapes of cellular phenotypic diversity in breast cancer xenografts and their impact on drug response," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22303-z
    DOI: 10.1038/s41467-021-22303-z
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