Patient-Derived Xenografts of Breast Cancer

Abstract

Patient-derived xenografts (PDX) of breast cancer, obtained from the engraftment of tumour samples into immunodeficient mice, are the most effective preclinical models for studying the biology of human breast cancer and for the evaluation of new anti-cancer treatments. Notably, breast cancer PDX preserve the phenotypic and molecular characteristics of the donor tumours and reproduce the diversity of breast cancer. This preservation of breast cancer biology involves a number of different aspects, including tumour architecture and morphology, patterns of genomic alterations and gene expression, mutational status, and intra-tumour heterogeneity. For these reasons, these models have a strong predictive value in the translation of cancer therapeutics into clinical settings and can be considered as powerful and clinically relevant research tools for the identification of new treatments, mechanisms of drug resistance, and predictive biomarkers. PDX models have also been successfully used to analyse breast cancer metastasis and persister cancer cells surviving chemotherapy. Limitations of breast cancer PDX include the lack of a human immune system and the low take rate, especially for estrogen receptor (ER) and HER2-positive subtypes.

Keywords: Breast cancer; Drug resistance; Drug response; PDX; Predictive biomarker.