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Updated: Oct 16, 2025
Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
Clinically Translatable Approaches of Inhibiting TGF-β to Target Cancer Stem Cells in TNBC
Andrew Sulaiman1,2, Sarah McGarry2, Sai Charan Chilumula1
1Department of Basic Science, Kansas City University, 1750 Independence Ave, Kansas City, MO 64106, USA.
Abstract:
Triple-negative breast cancer (TNBC) is a subtype of breast cancer that disproportionally accounts for the majority of breast cancer-related deaths due to the lack of specific targets for effective treatments. In this review, we highlight the complexity of the transforming growth factor-beta family (TGF-β) pathway and discuss how the dysregulation of the TGF-β pathway promotes oncogenic attributes in TNBC, which negatively affects patient prognosis. Moreover, we discuss recent findings highlighting TGF-β inhibition as a potent method to target mesenchymal (CD44+/CD24-) and epithelial (ALDHhigh) cancer stem cell (CSC) populations. CSCs are associated with tumorigenesis, metastasis, relapse, resistance, and diminished patient prognosis; however, due to differential signal pathway enrichment and plasticity, these populations remain difficult to target and persist as a major barrier barring successful therapy. This review highlights the importance of TGF-β as a driver of chemoresistance, radioresistance and reduced patient prognosis in breast cancer and highlights novel treatment strategies which modulate TGF-β, impede cancer progression and reduce the rate of resistance generation via targeting the CSC populations in TNBC and thus reducing tumorigenicity. Potential TGF-β inhibitors targeting based on clinical trials are summarized for further investigation, which may lead to the development of novel therapies to improve TNBC patient prognosis.
Insights
Triple-negative breast cancer (TNBC) lacks specific treatments. Targeting the transforming growth factor-beta (TGF-β) pathway, crucial in TNBC and cancer stem cells, offers a promising therapeutic strategy to improve patient outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Triple-negative breast cancer (TNBC) has a poor prognosis due to limited targeted therapies.
- The transforming growth factor-beta (TGF-β) pathway is frequently dysregulated in TNBC, promoting aggressive tumor characteristics.
- Cancer stem cells (CSCs) within TNBC contribute to treatment resistance, metastasis, and relapse.
Purpose of the Study:
- To review the role of the TGF-β pathway in TNBC pathogenesis and its impact on patient prognosis.
- To explore the potential of TGF-β inhibition as a therapeutic strategy against TNBC, particularly targeting CSCs.
- To summarize current clinical trial data on TGF-β inhibitors for TNBC treatment.
Main Methods:
- Literature review focusing on the TGF-β pathway in TNBC.
- Analysis of studies investigating TGF-β's role in CSC populations (mesenchymal and epithelial).
- Examination of clinical trial data for TGF-β inhibitors in breast cancer treatment.
Main Results:
- Dysregulation of the TGF-β pathway significantly contributes to oncogenic attributes and poor prognosis in TNBC.
- TGF-β inhibition shows potential in targeting both mesenchymal and epithelial CSCs, which are resistant to conventional therapies.
- CSCs are identified as key drivers of tumorigenesis, metastasis, and therapeutic resistance in TNBC.
Conclusions:
- Modulating the TGF-β pathway is a promising strategy to impede TNBC progression and overcome chemoresistance and radioresistance.
- Targeting CSCs via TGF-β inhibition may reduce tumorigenicity and the generation of treatment resistance.
- Further investigation of TGF-β inhibitors in clinical trials is warranted to develop novel therapies for improved TNBC patient outcomes.
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