Related Experiment Video

Updated: Jan 15, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
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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
PubMed

Insights

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.
Keywords:
cancerdrug resistancetransforming growth factor beta

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