Therapeutic Potentials of BDNF/TrkB in Breast Cancer; Current Status and Perspectives

Amir Tajbakhsh, Amin Mokhtari-Zaer, Mehdi Rezaee, Fahimeh Afzaljavan, Mehdi Rivandi, Seyed Mahdi Hassanian, Gordon A. Ferns, Alireza Pasdar*, Amir Avan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)

Abstract

Brain-derived neurotrophic factor (BDNF) is a potent neurotrophic factor that has been shown to stimulate breast cancer cell growth and metastasis via tyrosine kinase receptors TrkA, TrkB, and the p75NTR death receptor. The aberrant activation of BDNF/TrkB pathways can modulate several signaling pathways, including Akt/PI3K, Jak/STAT, NF-kB, UPAR/UPA, Wnt/β-catenin, and VEGF pathways as well as the ER receptor. Several microRNAs have been identified that are involved in the modulation of BDNF/TrkB pathways. These include miR-206, miR-204, MiR-200a/c, MiR-210, MiR-134, and MiR-191; and these may be of value as prognostic and predictive biomarkers for detecting patients at high risk of developing breast cancer. It has been also been demonstrated that a high expression of genes involved in the BDNF pathway in breast cancer is associated with poor clinical outcome and reduced survival of patients. Several approaches have been developed for targeting this pathway, for example TKr inhibitors (AZD6918, CEP-701) and RNA interference. The aim of the current review was to provide an overview of the role of BDNF/TrkB pathways in the pathogenesis of breast cancer and its value as a potential therapeutic target. J. Cell. Biochem. 118: 2502–2515, 2017.

Original languageEnglish
Pages (from-to)2502-2515
Number of pages14
JournalJournal of Cellular Biochemistry
Volume118
Issue number9
Early online date15 May 2017
DOIs
Publication statusPublished - 1 Sep 2017

Keywords

  • BRAIN-DERIVED NEUROTROPHIC FACTOR
  • BREAST CANCER
  • EPIGENETICS
  • PHARMACOLOGICAL MODULATORS
  • RISK FACTOR

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