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Updated: Jun 18, 2025
Orthotopic Transplantation of Breast Tumors as Preclinical Models for Breast Cancer
Published on: May 18, 2020
Leveraging preclinical models of metastatic breast cancer
Diego A Pedroza1, Yang Gao1, Xiang H-F Zhang1
1Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, United States of America; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, United States of America; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, United States of America.
Abstract:
Women that present to the clinic with established breast cancer metastases have limited treatment options. Yet, the majority of preclinical studies are actually not directed at developing treatment regimens for established metastatic disease. In this review we will discuss the current state of preclinical macro-metastatic breast cancer models, including, but not limited to syngeneic GEMM, PDX and xenografts. Challenges within these models which are often overlooked include fluorophore-immunogenic neoantigens, differences in experimental vs spontaneous metastasis and tumor heterogeneity. Furthermore, due to cell plasticity in the tumor immune microenvironment (TIME) of the metastatic landscape, the treatment efficacy of newly approved immune checkpoint blockade (ICB) may differ in metastatic sites as compared to primary localized tumors.
Insights
Preclinical models for established breast cancer metastasis are limited, hindering new treatment development. This review examines current models and challenges, including tumor heterogeneity and immune microenvironment differences, impacting treatment efficacy.
Area of Science:
- Oncology
- Translational Research
- Cancer Metastasis
Background:
- Established breast cancer metastasis presents limited therapeutic options.
- Preclinical research predominantly focuses on primary tumors, not established metastatic disease.
Purpose of the Study:
- To review current preclinical models for macro-metastatic breast cancer.
- To identify challenges and limitations within these models.
- To discuss implications for developing effective metastatic breast cancer treatments.
Main Methods:
- Review of existing literature on preclinical macro-metastatic breast cancer models.
- Analysis of syngeneic, GEMM, PDX, and xenograft models.
- Discussion of challenges including neoantigens, metastasis types, and tumor heterogeneity.
Main Results:
- Current preclinical models face challenges like fluorophore-immunogenic neoantigens and differences between experimental and spontaneous metastasis.
- Tumor heterogeneity and cell plasticity in the tumor immune microenvironment (TIME) of metastatic sites are significant concerns.
- The efficacy of immune checkpoint blockade (ICB) may vary between primary and metastatic tumors.
Conclusions:
- Improved preclinical models are crucial for developing effective treatments for metastatic breast cancer.
- Addressing model limitations, such as tumor heterogeneity and immune microenvironment dynamics, is essential.
- Further research is needed to understand how TIME plasticity affects treatment response in metastatic settings.
