BDNF and its signaling in cancer.

Abstract

Brain-derived neurotrophic factor (BDNF) belongs to the family of neurotrophic factors that can potentiallyincrease cancer cell growth, survival, proliferation, anoikis, and migration by tyrosine kinase receptors TrkB and thep75NTR 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 reviewaimed to provide an overview of the role of BDNF and its signaling in cancer. We searched a majormedical database, PubMed, to identify eligible studies for a narrative synthesis. Pathological examinationsdemonstrate BDNF overexpression in human cancer, notably involving the prostate, lung, breast, and underlyingtissues, associated with a higher death rate and poor prognosis. Therefore, measurement of BDNF, either foridentifying the disease or predicting response to therapy, can be helpful in cancer patients. Expression profilingstudies 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 correlatewith decreased BDNF expression in cancers. Clinical studies investigating the use of agents targeting BDNFreceptors and related signaling pathways and interfering with the related oncogenic effect, including Entrectinib,Larotrectinib, Cabozantinib, Repotrectinib, Lestaurtinib, and Selitrectinib, are in progress. The aberrantsignaling of BDNF is implicated in various cancers. Well-designed clinical trials are needed to clarify the BDNF rolein cancer progression and target it as a therapeutic method.