Targeting TGF-β signal transduction for fibrosis and cancer therapy

Mol Cancer. 2022 Apr 23;21(1):104. doi: 10.1186/s12943-022-01569-x.

Abstract

Transforming growth factor β (TGF-β) has long been identified with its intensive involvement in early embryonic development and organogenesis, immune supervision, tissue repair, and adult homeostasis. The role of TGF-β in fibrosis and cancer is complex and sometimes even contradictory, exhibiting either inhibitory or promoting effects depending on the stage of the disease. Under pathological conditions, overexpressed TGF-β causes epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) deposition, cancer-associated fibroblast (CAF) formation, which leads to fibrotic disease, and cancer. Given the critical role of TGF-β and its downstream molecules in the progression of fibrosis and cancers, therapeutics targeting TGF-β signaling appears to be a promising strategy. However, due to potential systemic cytotoxicity, the development of TGF-β therapeutics has lagged. In this review, we summarized the biological process of TGF-β, with its dual role in fibrosis and tumorigenesis, and the clinical application of TGF-β-targeting therapies.

Keywords: TGF-β; TGF-β signaling pathways; Targeted therapies.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Epithelial-Mesenchymal Transition
  • Extracellular Matrix / metabolism
  • Fibrosis / genetics
  • Fibrosis / metabolism
  • Humans
  • Neoplasms* / drug therapy
  • Neoplasms* / genetics
  • Signal Transduction
  • Transforming Growth Factor beta* / metabolism
  • Transforming Growth Factor beta* / therapeutic use

Substances

  • Transforming Growth Factor beta