Xiong Fei, Xiao Ben-Li, Wang Qi, Liu Kun, Wu Hong-Wei, Jing Chao, Tong Kui-Nan, Zhang Zhong-Tao, Guo Wei
Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
State Key Lab of Digestive Health, Beijing, China.
Mol Med. 2025 Aug 9;31(1):276. doi: 10.1186/s10020-025-01333-z.
As the first discovered member of the neurotrophin family, nerve growth factor (NGF) plays fundamental roles in peripheral sensory and sympathetic neuronal development and survival. Recent evidence reveals its tumour-promoting effects through increasing perineural invasion, which is correlated with poor clinical outcomes. The exact molecular mechanisms exhibit malignancy-specific differences and remain incompletely characterized.
This review compares mechanistic insights and therapeutic advancements regarding NGF signalling in neurological/psychological disorders with discoveries in oncological contexts. Functioning as a dual biomarker for neural integrity and pathological progression, NGF primarily exerts its effects via an interaction with the high-affinity tyrosine kinase receptor. Both molecules are frequently overexpressed in malignant tissues. NGF orchestrates tissue regeneration and tumourigenesis through the activation of conserved neurotrophin pathways and downstream proliferative cascades, some of which participate in regulating the expression and secretion of NGF in turn. In practical applications, in addition to acting as an antiproliferative target, NGF could be utilized in psychological management, antinociceptive treatment, and wound healing.
Systemic NGF-targeted therapies have significant articular and neurological toxicity, indicating the critical need for localized intervention strategies depending on the expression level of NGF and TrkA to balance antitumour efficacy with protective requirements for nerve structures and innervation.
作为神经营养因子家族中首个被发现的成员,神经生长因子(NGF)在周围感觉和交感神经元的发育与存活中发挥着重要作用。最近的证据显示,它通过增加神经周围浸润发挥促肿瘤作用,而这与不良临床预后相关。确切的分子机制存在恶性肿瘤特异性差异,且仍未完全明确。
本综述比较了神经生长因子信号传导在神经/心理疾病中的机制见解和治疗进展,以及在肿瘤学背景下的相关发现。作为神经完整性和病理进展的双重生物标志物,神经生长因子主要通过与高亲和力酪氨酸激酶受体相互作用发挥作用。这两种分子在恶性组织中经常过度表达。神经生长因子通过激活保守的神经营养因子途径和下游增殖级联反应来协调组织再生和肿瘤发生,其中一些反过来参与调节神经生长因子的表达和分泌。在实际应用中,除了作为抗增殖靶点外,神经生长因子还可用于心理管理、抗伤害感受治疗和伤口愈合。
全身性神经生长因子靶向治疗具有显著的关节和神经毒性,这表明迫切需要根据神经生长因子和酪氨酸激酶受体A(TrkA)的表达水平制定局部干预策略,以平衡抗肿瘤疗效与对神经结构和神经支配的保护需求。