Mohammad Malekan1,2, Sasan Salehi Nezamabadi3,4, Elham Samami3,5, Mehdi Mohebalizadeh6,7, Amene Saghazadeh3,8, Nima Rezaei9,10,11. 1. Systematic Review and Meta-Analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Sari, Iran. 2. Student Research Committee, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. 3. Systematic Review and Meta-Analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Tehran, Iran. 4. School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. 5. Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran. 6. Systematic Review and Meta-Analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Urmia, Iran. 7. Student Research Center, Urmia University of Medical Sciences, Urmia, Iran. 8. Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Dr. Qarib St, Keshavarz Blvd, Tehran, 14194, Iran. 9. Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Dr. Qarib St, Keshavarz Blvd, Tehran, 14194, Iran. rezaei_nima@tums.ac.ir. 10. Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Tehran, Iran. rezaei_nima@tums.ac.ir. 11. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. rezaei_nima@tums.ac.ir.
Abstract
PURPOSE: Brain-derived neurotrophic factor (BDNF) belongs to the family of neurotrophic factors that can potentially increase cancer cell growth, survival, proliferation, anoikis, and migration by tyrosine kinase receptors TrkB and the p75NTR death receptor. The activation of BDNF/TrkB pathways leads to several downstream signaling pathways, including PI3K/Akt, Jak/STAT, PLCγ, Ras-Raf-MEK-ERK, NF-kB, and transactivation of EGFR. The current review aimed to provide an overview of the role of BDNF and its signaling in cancer. METHODS: We searched a major medical database, PubMed, to identify eligible studies for a narrative synthesis. RESULTS: Pathological examinations demonstrate BDNF overexpression in human cancer, notably involving the prostate, lung, breast, and underlying tissues, associated with a higher death rate and poor prognosis. Therefore, measurement of BDNF, either for identifying the disease or predicting response to therapy, can be helpful in cancer patients. Expression profiling studies have recognized the role of microRNAs (miR) in modulating BDNF/TrkB pathways, such as miR-101, miR-107, miR-134, miR-147, miR-191, miR-200a/c, miR-204, miR-206, miR-210, miR-214, miR-382, miR-496, miR-497, miR-744, and miR-10a-5p, providing a potential biological mechanism by which targeted therapies may correlate with decreased BDNF expression in cancers. Clinical studies investigating the use of agents targeting BDNF receptors and related signaling pathways and interfering with the related oncogenic effect, including Entrectinib, Larotrectinib, Cabozantinib, Repotrectinib, Lestaurtinib, and Selitrectinib, are in progress. CONCLUSION: The aberrant signaling of BDNF is implicated in various cancers. Well-designed clinical trials are needed to clarify the BDNF role in cancer progression and target it as a therapeutic method.
PURPOSE: Brain-derived neurotrophic factor (BDNF) belongs to the family of neurotrophic factors that can potentially increase cancer cell growth, survival, proliferation, anoikis, and migration by tyrosine kinase receptors TrkB and the p75NTR death receptor. The activation of BDNF/TrkB pathways leads to several downstream signaling pathways, including PI3K/Akt, Jak/STAT, PLCγ, Ras-Raf-MEK-ERK, NF-kB, and transactivation of EGFR. The current review aimed to provide an overview of the role of BDNF and its signaling in cancer. METHODS: We searched a major medical database, PubMed, to identify eligible studies for a narrative synthesis. RESULTS: Pathological examinations demonstrate BDNF overexpression in human cancer, notably involving the prostate, lung, breast, and underlying tissues, associated with a higher death rate and poor prognosis. Therefore, measurement of BDNF, either for identifying the disease or predicting response to therapy, can be helpful in cancer patients. Expression profiling studies have recognized the role of microRNAs (miR) in modulating BDNF/TrkB pathways, such as miR-101, miR-107, miR-134, miR-147, miR-191, miR-200a/c, miR-204, miR-206, miR-210, miR-214, miR-382, miR-496, miR-497, miR-744, and miR-10a-5p, providing a potential biological mechanism by which targeted therapies may correlate with decreased BDNF expression in cancers. Clinical studies investigating the use of agents targeting BDNF receptors and related signaling pathways and interfering with the related oncogenic effect, including Entrectinib, Larotrectinib, Cabozantinib, Repotrectinib, Lestaurtinib, and Selitrectinib, are in progress. CONCLUSION: The aberrant signaling of BDNF is implicated in various cancers. Well-designed clinical trials are needed to clarify the BDNF role in cancer progression and target it as a therapeutic method.
Authors: Christy W H Au; Michelle K Y Siu; Xiaoyun Liao; Esther S Y Wong; Hextan Y S Ngan; Kar Fai Tam; Dominic C W Chan; Queeny K Y Chan; Annie N Y Cheung Journal: Cancer Lett Date: 2009-08-28 Impact factor: 8.679