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Updated: Oct 9, 2025

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

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TGF-β Signaling and Resistance to Cancer Therapy

Maoduo Zhang1,2,3, Ying Yi Zhang4, Yongze Chen5

  • 1State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

Frontiers in Cell and Developmental Biology
|December 17, 2021
PubMed

Insights

The transforming growth factor beta (TGF-β) pathway has a dual role in cancer, acting as a double-edged sword. Targeting TGF-β may overcome drug resistance in cancer therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Signaling Pathways

Background:

  • The transforming growth factor beta (TGF-β) pathway exhibits context-dependent roles in cancer, inhibiting early tumorigenesis but promoting advanced cancer progression.
  • TGF-β signaling is implicated in epithelial-mesenchymal transition (EMT), invasion, and metastasis.
  • Clinical trial results for TGF-β inhibitors have been inconsistent, indicating incomplete understanding of its functions in human cancers.

Purpose of the Study:

  • To explore the multifaceted roles of TGF-β signaling in cancer.
  • To investigate the involvement of TGF-β in mediating resistance to various cancer therapies.
  • To evaluate the potential of combining anti-TGF-β therapy with existing cancer treatments.

Main Methods:

  • Review of existing literature on TGF-β signaling in cancer.
  • Analysis of preclinical and clinical data regarding TGF-β inhibitors.
  • Examination of emerging evidence linking TGF-β to drug resistance mechanisms.

Main Results:

  • TGF-β acts as a "double-edged sword" in cancer, with complex effects on tumor initiation and progression.
  • Emerging evidence suggests TGF-β signaling is a critical factor in resistance to chemotherapy, targeted therapy, and immunotherapy.
  • Inconsistent clinical outcomes highlight the need for further research into TGF-β's precise roles.

Conclusions:

  • The intricate roles of TGF-β in human cancers require deeper investigation.
  • TGF-β signaling is a significant contributor to multiple drug resistance in cancer.
  • Combination therapy involving anti-TGF-β agents presents a promising strategy for treating therapy-resistant cancers.
Keywords:
TGF-βTGF-β pathwaychemotherapy resistanceimmunotherapy resistancetargeted therapy resistance

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