The therapeutic potential of blocking the activin signalling pathway

Cytokine Growth Factor Rev. 2013 Oct;24(5):477-84. doi: 10.1016/j.cytogfr.2013.04.006. Epub 2013 Jun 18.

Abstract

Members of the transforming growth factor β (TGF-β) family regulate fundamental physiological process, such as cell growth, differentiation and apoptosis. As a result, defects in this pathway have been linked to uncontrolled proliferation and cancer progression. Here we explore the signal transduction mechanism of TGF-β focusing on therapeutic intervention in human diseases. Like TGF-β, another member of the TGF-β superfamily, activin has been proven to play an important role in maintenance of tissue homeostasis and dysregulation leads to disease. Several studies showed elevated levels of activin are responsible for the development of gonadal tumours and a cachexia-like weight loss syndrome. Discussing the recent advances in approaches developed to antagonise the activin pathway and the encouraging results obtained in animal models, this review presents a therapeutic rationale for targeting the activin pathway in conditions such as cachexia, neuromuscular and/or musculoskeletal disorders.

Keywords: Activin antagonism; Cancer associated cachexia; TGF-β; TGF-β antagonism.

Publication types

  • Review

MeSH terms

  • Activins / antagonists & inhibitors*
  • Activins / genetics
  • Activins / metabolism
  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Cachexia / drug therapy*
  • Cachexia / genetics
  • Cachexia / metabolism
  • Cell Proliferation / drug effects
  • Humans
  • Musculoskeletal Diseases / drug therapy*
  • Musculoskeletal Diseases / genetics
  • Musculoskeletal Diseases / metabolism
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neoplasms, Gonadal Tissue / drug therapy*
  • Neoplasms, Gonadal Tissue / genetics
  • Neoplasms, Gonadal Tissue / metabolism
  • Neuromuscular Diseases / drug therapy*
  • Neuromuscular Diseases / genetics
  • Neuromuscular Diseases / metabolism
  • Signal Transduction / drug effects*
  • Signal Transduction / genetics
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism

Substances

  • Antineoplastic Agents
  • Neoplasm Proteins
  • Transforming Growth Factor beta
  • Activins