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Updated: Aug 4, 2025
High-Throughput Dissociation and Orthotopic Implantation of Breast Cancer Patient-Derived Xenografts
Published on: December 20, 2024
Development and characterization of a patient‑derived orthotopic xenograft of therapy‑resistant breast cancer
Ramesh Butti1, Prachi Kapse1, Garima Bhadauriya1
1Laboratory of Tumor Biology, Angiogenesis and Nanomedicine Research, National Centre for Cell Science, Pune, Maharashtra 411007, India.
Abstract:
Numerous years of cell line‑based studies have enhanced the current understanding of cancer and its treatment. However, limited success has been achieved in treating hormone receptor‑positive, HER2‑negative metastatic breast cancers that are refractory to treatment. The majority of cancer cell lines are unsuitable for use as pre‑clinical models that mimic this critical and often fatal clinical type, since they are derived from treatment‑naive or non‑metastatic breast cancer cases. The aim of the present study was to develop and characterize patient‑derived orthotopic xenografts (PDOXs) from patients with endocrine hormone receptor‑positive, HER2‑negative metastatic breast cancer who had relapsed on therapy. A patient who progressed on endocrine hormone therapy provided her tumor via a biobank. This tumor was implanted in mice. It was then serially passaged by implanting PDOX tumor fragments into another set of mice to develop further generations of PDOXs. These tissues were characterized using various histological and biochemical techniques. Histological, immunofluorescence and western blot analyses indicated that the PDOX tumors retained a similar morphology, histology and subtype‑specific molecular features to that of the patient's tumor. The present study successfully established PDOXs of hormone‑resistant breast cancer and characterized them in comparison with those derived from the original breast cancer tissue of the patient. The data highlight the reliability and usefulness of PDOX models for studies of biomarker discovery and preclinical drug screening. The present study was registered with the clinical trial registry of India (CTRI; registration no. CTRI/2017/11/010553; registered on 17/11/2017).
Insights
Patient-derived orthotopic xenografts (PDOXs) were developed from hormone-resistant breast cancer. These models accurately reflect patient tumors, proving useful for preclinical drug screening and biomarker discovery.
Area of Science:
- Oncology
- Translational Research
- Cancer Models
Background:
- Hormone receptor-positive, HER2-negative metastatic breast cancer often becomes refractory to treatment.
- Existing cell line models inadequately represent this aggressive cancer subtype.
- There is a critical need for better preclinical models for this specific breast cancer type.
Purpose of the Study:
- To develop and characterize patient-derived orthotopic xenografts (PDOXs) from treatment-resistant breast cancer.
- To assess the fidelity of PDOX models compared to the original patient tumors.
- To evaluate the utility of PDOXs for preclinical research.
Main Methods:
- Tumor tissue from a patient with metastatic, hormone-resistant breast cancer was used.
- Tumor fragments were implanted into mice and serially passaged to create multiple generations of PDOXs.
- Histological, immunofluorescence, and western blot analyses were performed for characterization.
Main Results:
- Established PDOX models retained the original patient tumor's morphology, histology, and molecular features.
- Characterization confirmed the subtype-specific molecular characteristics were maintained across passages.
- PDOX models demonstrated high fidelity to the patient's original tumor.
Conclusions:
- Successfully established and characterized PDOXs from hormone-resistant breast cancer.
- PDOX models are reliable and valuable for preclinical drug screening and biomarker discovery in this cancer type.
- These models offer a more accurate representation of patient tumors than traditional cell lines.
