Targeting TGF-β in prostate cancer: Therapeutic possibilities during tumor progression

Elisabeth Jones, Hong Pu, Natasha Kyprianou

Research output: Contribution to journalReview article

70 Citations (Scopus)

Abstract

Background : TGF-β regulates prostate growth by inhibiting epithelial cell proliferation and inducing apoptosis through eliciting a dynamic signaling pathway. In metastatic prostate cancer, however, TGF-β serves as a tumor promoter. TGF-β engages Smad-dependent and Smad-independent mechanisms to exert its action. During prostate tumorigenesis, prostate cells exhibit loss or mutation of TGF-β transmembrane receptors. Increased production of TGF-β causes immunosuppression, extracellular matrix degrada tion, epithelia to mesenchymal transition and angiogenesis that promotes tumor cell invasion and metastasis. Objective : The molecular basis for effective therapeutic targeting of TGF-β must be directed towards the double-edge-sword nature of the cytokine: Inhibiting the TGF-β tumor promoter capabilities in advanced metastatic prostate cancer, although retaining the growthinhibitory abilities exhibited in early stages of prostate tumorigenesis. Results/conclusion : The current understanding of the therapeutic possibilities of targeting TGF-β signaling during prostate tumor progression is built on preclinical studies. Studies targeting TGF-β signaling pathway for the treatment of several human malignancies include the use of neutralizing antibodies, antisense oligonucelotides and small molecule inhibitors of kinase activity of the receptor complex. This review focuses on exploiting the therapeutic potential of targeting TGF-β signaling in the context of its contribution to prostate cancer initiation and progression to metastasis.

Original languageEnglish
Pages (from-to)227-234
Number of pages8
JournalExpert Opinion on Therapeutic Targets
Volume13
Issue number2
DOIs
Publication statusPublished - Feb 1 2009

Keywords

  • Apoptosis signaling
  • Prostate cancer
  • Smad-targeting
  • TGF-β

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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