Stromal Characteristics and Impact on New Therapies for Metastatic Triple-Negative Breast Cancer
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...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/14/5/1238 |
| _version_ | 1797475490137636864 |
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| author | Shelby A. Fertal Johanna E. Poterala Suzanne M. Ponik Kari B. Wisinski |
| author_facet | Shelby A. Fertal Johanna E. Poterala Suzanne M. Ponik Kari B. Wisinski |
| author_sort | Shelby A. Fertal |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T20:45:51Z |
| format | Article |
| id | doaj.art-9409c16e770642fe86e59a960492e26f |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T20:45:51Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-9409c16e770642fe86e59a960492e26f2023-11-23T22:47:59ZengMDPI AGCancers2072-66942022-02-01145123810.3390/cancers14051238Stromal Characteristics and Impact on New Therapies for Metastatic Triple-Negative Breast CancerShelby A. Fertal0Johanna E. Poterala1Suzanne M. Ponik2Kari B. Wisinski3University of Wisconsin (UW) Carbone Cancer Center, Madison, WI 53705, USAUniversity of Wisconsin (UW) Carbone Cancer Center, Madison, WI 53705, USAUniversity of Wisconsin (UW) Carbone Cancer Center, Madison, WI 53705, USAUniversity of Wisconsin (UW) Carbone Cancer Center, Madison, WI 53705, USAThe 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.https://www.mdpi.com/2072-6694/14/5/1238triple-negative breast cancer (TNBC)immunotherapyantibody–drug conjugates (ADCs)tumor microenvironmentstromaextracellular matrix |
| spellingShingle | Shelby A. Fertal Johanna E. Poterala Suzanne M. Ponik Kari B. Wisinski Stromal Characteristics and Impact on New Therapies for Metastatic Triple-Negative Breast Cancer Cancers triple-negative breast cancer (TNBC) immunotherapy antibody–drug conjugates (ADCs) tumor microenvironment stroma extracellular matrix |
| title | Stromal Characteristics and Impact on New Therapies for Metastatic Triple-Negative Breast Cancer |
| title_full | Stromal Characteristics and Impact on New Therapies for Metastatic Triple-Negative Breast Cancer |
| title_fullStr | Stromal Characteristics and Impact on New Therapies for Metastatic Triple-Negative Breast Cancer |
| title_full_unstemmed | Stromal Characteristics and Impact on New Therapies for Metastatic Triple-Negative Breast Cancer |
| title_short | Stromal Characteristics and Impact on New Therapies for Metastatic Triple-Negative Breast Cancer |
| title_sort | stromal characteristics and impact on new therapies for metastatic triple negative breast cancer |
| topic | triple-negative breast cancer (TNBC) immunotherapy antibody–drug conjugates (ADCs) tumor microenvironment stroma extracellular matrix |
| url | https://www.mdpi.com/2072-6694/14/5/1238 |
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