Targeting the transforming growth factor-beta signaling pathway in human cancer

Expert Opin Investig Drugs. 2010 Jan;19(1):77-91. doi: 10.1517/13543780903382609.


The transforming growth factor-ss (TGF-beta) signaling pathway plays a pivotal role in diverse cellular processes. TGF-beta switches its role from a tumor suppressor in normal or dysplastic cells to a tumor promoter in advanced cancers. It is widely believed that the Smad-dependent pathway is involved in TGF-beta tumor-suppressive functions, whereas activation of Smad-independent pathways, coupled with the loss of tumor-suppressor functions of TGF-beta, is important for its pro-oncogenic functions. TGF-beta signaling has been considered a useful therapeutic target. The discovery of oncogenic actions of TGF-beta has generated a great deal of enthusiasm for developing TGF-beta signaling inhibitors for the treatment of cancer. The challenge is to identify the group of patients where targeted tumors are not only refractory to TGF-beta-induced tumor suppressor functions but also responsive to the tumor-promoting effects of TGF-beta. TGF-beta pathway inhibitors, including small and large molecules, have now entered clinical trials. Preclinical studies with these inhibitors have shown promise in a variety of different tumor models. Here, we focus on the mechanisms of signaling and specific targets of the TGF-beta pathway that are critical effectors of tumor progression and invasion. This report also examines the therapeutic intervention of TGF-ss signaling in human cancers.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Clinical Trials as Topic
  • Drug Discovery
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Oligonucleotides, Antisense / administration & dosage
  • Oligonucleotides, Antisense / adverse effects
  • Oligonucleotides, Antisense / pharmacology
  • Oligonucleotides, Antisense / therapeutic use
  • Signal Transduction / drug effects*
  • Small Molecule Libraries / administration & dosage
  • Small Molecule Libraries / pharmacology
  • Small Molecule Libraries / therapeutic use
  • Transforming Growth Factor beta / antagonists & inhibitors*


  • Antineoplastic Agents
  • Oligonucleotides, Antisense
  • Small Molecule Libraries
  • Transforming Growth Factor beta