Related Experiment Video
Updated: Sep 30, 2025
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Stromal Characteristics and Impact on New Therapies for Metastatic Triple-Negative Breast Cancer
Shelby A Fertal1,2, Johanna E Poterala1,3, Suzanne M Ponik1,2
1University of Wisconsin (UW) Carbone Cancer Center, Madison, WI 53705, USA.
Abstract:
The heterogenous nature of triple-negative breast cancer (TNBC) is an underlying factor in therapy resistance, metastasis, and overall poor patient outcome. The lack of hormone and growth factor receptors lends to the use of chemotherapy as the first-line treatment for TNBC. However, the failure of chemotherapy demonstrates the need to develop novel immunotherapies, antibody-drug conjugates (ADCs), and other tumor- and stromal-targeted therapeutics for TNBC patients. The potential for stromal-targeted therapy is driven by studies indicating that the interactions between tumor cells and the stromal extracellular matrix (ECM) activate mechanisms of therapy resistance. Here, we will review recent outcomes from clinical trials targeting metastatic TNBC with immunotherapies aimed at programed death ligand-receptor interactions, and ADCs specifically linked to trophoblast cell surface antigen 2 (Trop-2). We will discuss how biophysical and biochemical cues from the ECM regulate the pathophysiology of tumor and stromal cells toward a pro-tumor immune environment, therapy resistance, and poor TNBC patient outcome. Moreover, we will highlight how ECM-mediated resistance is motivating the development of new stromal-targeted therapeutics with potential to improve therapy for this disease.
Insights
Triple-negative breast cancer (TNBC) is hard to treat due to its varied nature. New therapies targeting the tumor microenvironment, like immunotherapies and antibody-drug conjugates, show promise for improving outcomes.
Area of Science:
- Oncology
- Immunology
- Biochemistry
Background:
- Triple-negative breast cancer (TNBC) is characterized by heterogeneity, leading to therapy resistance, metastasis, and poor patient outcomes.
- Chemotherapy is the primary treatment, but its limitations necessitate the development of novel therapeutic strategies for TNBC.
Purpose of the Study:
- To review recent clinical trial outcomes for metastatic TNBC, focusing on immunotherapies and antibody-drug conjugates (ADCs).
- To discuss the role of the extracellular matrix (ECM) in regulating tumor-stromal cell interactions and driving therapy resistance in TNBC.
- To highlight the development of novel stromal-targeted therapeutics to overcome ECM-mediated resistance.
Main Methods:
- Review of clinical trial data for immunotherapies targeting PD-1/PD-L1 interactions and ADCs targeting Trop-2 in metastatic TNBC.
- Analysis of biophysical and biochemical cues from the ECM influencing tumor and stromal cell pathophysiology.
- Discussion of emerging stromal-targeted therapeutic strategies.
Main Results:
- Immunotherapies and ADCs targeting Trop-2 demonstrate potential in clinical trials for metastatic TNBC.
- ECM-derived cues promote a pro-tumorigenic immune microenvironment and contribute to therapy resistance.
- Stromal-targeted therapies are emerging as a promising approach to combat ECM-mediated resistance.
Conclusions:
- The heterogeneity of TNBC and ECM interactions present significant challenges, but novel immunotherapies and ADCs offer new hope.
- Understanding ECM's role in resistance is crucial for developing more effective TNBC treatments.
- Targeting the tumor microenvironment, including stromal components, is key to improving therapeutic outcomes for TNBC patients.
More Related Videos
07:03Isolation and Functional Assessment of Human Breast Cancer Stem Cells from Cell and Tissue Samples
Published on: October 2, 2020
09:44Generation of Organ-conditioned Media and Applications for Studying Organ-specific Influences on Breast Cancer Metastatic Behavior
Published on: June 13, 2016
Related Concept Videos
02:30Metastasis
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
02:40Cancer Stem Cells and Tumor Maintenance
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...