Advances in Regulating Tumorigenicity and Metastasis of Cancer Through TrkB Signaling

The clinical pathology of various human malignancies is supported by tropomyosin receptor kinase (Trk) B TrkB which is a specific binding receptor of the brain-derived neurotrophic factor (BDNF). TrkB and TrkB fusion proteins have been observed to be over-expressed in many cancer patients. Moreover, these proteins have been observed in multiple types of cells. A few signaling pathways can be modulated by the abnormal activation of the BDNF/TrkB pathway. These signaling pathways include PI3K/Akt pathway, transactivation of EGFR, phospholipase C-gamma (PLCγ) pathway, Ras-Raf-MEK-ERK pathway, Jak/STAT pathway, and nuclear factor kappalight- chain-enhancer of activated B cells (NF-kB) pathway. The BDNF/TrkB pathway, when overexpressed in tumors, is correlated with reduced clinical prognosis and short survival time of patients. Targeting the BDNF/TrkB pathway and the use of Trk inhibitors, such as entrectinib, larotrectinib, etc. are promising methods for targeted therapy of tumors. The present review provides an overview of the role of the TrkB pathway in the pathogenesis of cancer and its value as a potential therapeutic target.