TrkB/BDNF Signaling Could Be a New Therapeutic Target for Pancreatic Cancer

Anticancer Res. 2021 Aug;41(8):4047-4052. doi: 10.21873/anticanres.15205.


Background/aim: Tropomyosin-related kinase B (TrkB)/brain-derived neurotrophic factor (BDNF) signaling plays a role in inducing malignant phenotypes in several aggressive types of cancers. To create a conclusive therapy targeting TrkB/BDNF signaling in solid refractory cancers, the biological significance of TrkB/BDNF signaling was analyzed in pancreatic ductal adenocarcinoma (PDAC) cells.

Materials and methods: Three PDAC cell lines were used as target cells to investigate proliferation and invasiveness. Small interfering RNA (siRNA) and the TrkB tyrosine kinase inhibitor k252a were used as TrkB/BDNF signaling inhibitors.

Results: All PDAC cell lines expressed TrkB and BDNF. When TrkB and BDNF were inhibited by siRNA or k252a, the invasiveness of PANC-1 and SUIT-2 cells significantly decreased. When TrkB was inhibited by siRNA or k252a, proliferation was significantly inhibited in PDAC cells.

Conclusion: TrkB/BDNF signaling may be a new therapeutic target for PDAC. Therapies targeting TrkB/BDNF signaling may be a conclusive cancer therapy for refractory solid cancer.

Keywords: BDNF; TrkB; invasion; pancreatic cancer; proliferation.

MeSH terms

  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Carbazoles / pharmacology
  • Carcinoma, Pancreatic Ductal / metabolism*
  • Carcinoma, Pancreatic Ductal / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Humans
  • Indole Alkaloids / pharmacology
  • Membrane Glycoproteins / antagonists & inhibitors
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Protein Kinase Inhibitors / pharmacology
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Receptor, trkB / antagonists & inhibitors
  • Receptor, trkB / genetics
  • Receptor, trkB / metabolism*
  • Signal Transduction / drug effects


  • Brain-Derived Neurotrophic Factor
  • Carbazoles
  • Indole Alkaloids
  • Membrane Glycoproteins
  • Protein Kinase Inhibitors
  • RNA, Small Interfering
  • BDNF protein, human
  • staurosporine aglycone
  • Receptor, trkB
  • tropomyosin-related kinase-B, human