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Updated: Jan 15, 2026
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Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
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Diverse Biological Processes Contribute to Transforming Growth Factor β-Mediated Cancer Drug Resistance
James P Heiserman1, Rosemary J Akhurst1,2,3
1Helen Diller Family Comprehensive Cancer Center, University of California San Francisco (UCSF), San Francisco, CA 94143, USA.
Cells
|October 15, 2025
Summary
Transforming growth factor-beta (TGF-β) signaling drives cancer therapy resistance by promoting drug efflux, DNA repair, and immune suppression. Targeting TGF-β pathways is crucial for overcoming treatment obstacles and improving patient outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Therapy resistance is a significant challenge in cancer treatment.
- Transforming growth factor-beta (TGF-β) signaling is implicated in resistance across various cancers.
- Cancer therapies can paradoxically increase TGF-β release, exacerbating resistance.
Purpose of the Study:
- To elucidate the molecular mechanisms by which TGF-β signaling contributes to cancer therapy resistance.
- To highlight the role of TGF-β in mediating resistance through various cellular and microenvironmental changes.
- To emphasize the need for further research into TGF-β targeted strategies for overcoming drug resistance.
Main Methods:
- Review and synthesis of existing literature on TGF-β signaling in cancer therapy resistance.
- Analysis of molecular mechanisms including gene expression, protein signaling, and cellular processes.
- Examination of TGF-β's impact on the tumor microenvironment and immune cells.
Main Results:
- TGF-β signaling promotes resistance via drug efflux pumps, enhanced DNA repair, and extracellular matrix remodeling.
- It activates pro-survival pathways (EGFR, Bcl-2, AKT-mTOR) and drives epithelial-to-mesenchymal transition, leading to tumor heterogeneity and stem-like states.
- In the tumor microenvironment, TGF-β fosters immunosuppression by activating cancer-associated fibroblasts and inhibiting cytotoxic immune cells while promoting regulatory cells.
Conclusions:
- TGF-β signaling is a critical driver of multifaceted cancer therapy resistance.
- Understanding these mechanisms is essential for developing novel therapeutic strategies.
- Targeting TGF-β pathways offers a promising avenue for combination therapies and overcoming drug resistance.
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