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Updated: Apr 23, 2026
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Highly adaptable triple-negative breast cancer cells as a functional model for testing anticancer agents
Balraj Singh1, Anna Shamsnia1, Milan R Raythatha1
1Department of Surgical Oncology, and Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Abstract:
A major obstacle in developing effective therapies against solid tumors stems from an inability to adequately model the rare subpopulation of panresistant cancer cells that may often drive the disease. We describe a strategy for optimally modeling highly abnormal and highly adaptable human triple-negative breast cancer cells, and evaluating therapies for their ability to eradicate such cells. To overcome the shortcomings often associated with cell culture models, we incorporated several features in our model including a selection of highly adaptable cancer cells based on their ability to survive a metabolic challenge. We have previously shown that metabolically adaptable cancer cells efficiently metastasize to multiple organs in nude mice. Here we show that the cancer cells modeled in our system feature an embryo-like gene expression and amplification of the fat mass and obesity associated gene FTO. We also provide evidence of upregulation of ZEB1 and downregulation of GRHL2 indicating increased epithelial to mesenchymal transition in metabolically adaptable cancer cells. Our results obtained with a variety of anticancer agents support the validity of the model of realistic panresistance and suggest that it could be used for developing anticancer agents that would overcome panresistance.
Insights
Developing a new model for panresistant cancer cells is crucial for effective solid tumor therapies. This study presents a novel approach to model and test treatments against these adaptable, rare cancer cells.
Area of Science:
- Oncology
- Cancer Biology
- Genetics
Background:
- Developing effective therapies for solid tumors is hindered by the challenge of modeling rare, panresistant cancer cell subpopulations.
- Existing cell culture models often fail to adequately represent the complexity and adaptability of these aggressive cancer cells.
Purpose of the Study:
- To develop and validate an optimal model for human triple-negative breast cancer cells with panresistance.
- To evaluate the efficacy of various anticancer agents in eradicating these highly adaptable cancer cells.
Main Methods:
- Selected highly adaptable cancer cells based on survival through a metabolic challenge.
- Analyzed gene expression, including embryo-like patterns and amplification of the FTO gene.
- Assessed epithelial to mesenchymal transition markers (ZEB1 and GRHL2).
- Tested a variety of anticancer agents against the developed model.
Main Results:
- The modeled cancer cells exhibited embryo-like gene expression and FTO gene amplification.
- Evidence of increased epithelial to mesenchymal transition was observed (ZEB1 upregulation, GRHL2 downregulation).
- Metabolically adaptable cancer cells demonstrated efficient metastasis in previous studies.
- Anticancer agents showed varying efficacy, supporting the model's validity.
Conclusions:
- The developed model effectively represents realistic panresistance in cancer cells.
- This model can be utilized for the development of novel anticancer agents designed to overcome panresistance.
- Further research into targeting these adaptable cancer cell populations is warranted.
