Oncogenic role of the brain‑derived neurotrophic factor‑TrkB axis with a focus on gallbladder cancer (Review)

Bansal,Shivani; Hedau,Suresh T.; Sengupta,Shinjinee; Sakhuja,Puja; Agarwal,Anil; Singh,Sompal; Chopra,Ratna; Gupta,Sanjay; Singh,Priti; Andley,Manoj; Gupta,Ruchika

doi:10.3892/mmr.2025.13570

Oncogenic role of the brain‑derived neurotrophic factor‑TrkB axis with a focus on gallbladder cancer (Review)

Authors:
- Shivani Bansal
- Suresh T. Hedau
- Shinjinee Sengupta
- Puja Sakhuja
- Anil Agarwal
- Sompal Singh
- Ratna Chopra
- Sanjay Gupta
- Priti Singh
- Manoj Andley
- Ruchika Gupta
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Affiliations: Division of Cytopathology, ICMR‑National Institute of Cancer Prevention and Research, Noida, Uttar Pradesh 201301, India, Division of Molecular Oncology, ICMR‑National Institute of Cancer Prevention and Research, Noida, Uttar Pradesh 201301, India, Amity Institute of Molecular Medicine and Stem Cell Research, Amity University, Noida, Uttar Pradesh 201301, India, Department of Pathology, GB Pant Institute of Postgraduate Medical Education and Research, Delhi 110002, India, Department of Gastrointestinal Surgery, GB Pant Institute of Postgraduate Medical Education and Research, Delhi 110002, India, Department of Pathology, North DMC Medical College and Hindu Rao Hospital, Delhi 110007, India, Department of Surgery, North DMC Medical College and Hindu Rao Hospital, Delhi 110007, India, Department of Pathology, Lady Hardinge Medical College and Associated Hospitals, New Delhi, Delhi 110001, India, Department of Surgery, Lady Hardinge Medical College and Associated Hospitals, New Delhi, Delhi 110001, India
Published online on: May 19, 2025 https://doi.org/10.3892/mmr.2025.13570
Article Number: 205

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Abstract

Brain‑derived neurotrophic factor (BDNF) belongs to the neurotrophin family of growth factors that regulate the development of the central nervous system during fetal growth. Apart from its role in neurogenesis, BDNF, along with its high‑affinity receptor tropomyosin‑related receptor kinase B (TrkB), serves a key role in the pathogenesis of several tumors such as breast, cervical and colorectal cancer, and gliomas. The oncogenic effects of BDNF and TrkB upregulation, including effects on the aggressiveness, metastatic potential and resistance to standard chemotherapeutic agents, are mediated by the downstream activation of the PI3K/Akt pathway, EGFR activation and MAPK pathways. In view of the key role served by BDNF and TrkB in various steps of oncogenesis, there have been attempts to develop inhibitors of the TrkB receptor to block the effects of BDNF upregulation, and these have shown promising results. The role of the BDNF‑TrkB pathway in the pathogenesis of gallbladder cancer (GBC), a biliary tract malignancy with high mortality, has still not been fully elucidated. Immunohistochemical expression of TrkB at the invasive front of GBC has been demonstrated along with the growth inhibitory effect of TrkB siRNA on GBC cell lines, suggesting the role of this pathway in the aggressiveness of GBC. The present review explores the mechanisms of action of the BDNF‑TrkB axis, focusing on GBC, in an attempt to provide future research directions for delineating the role of this pathway in the pathogenesis of GBC and the potential therapeutic implications.

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