Trk kinase inhibitors as new treatments for cancer and pain

Background: Tropomyosin-related kinases (Trks) are a family of receptor tyrosine kinases activated by neurotrophins. Trks play important roles in pain sensation as well as tumour cell growth and survival signaling. Thus, inhibitors of Trk receptor kinases might provide targeted treatments for pain and cancer. Objective: This paper reviews those patent applications since 2002 claiming small-molecule inhibitors of Trk receptor kinases. Methods: Primary literature and patents were searched with SciFinder and Google Scholar. Patents were selected based on their relevance to Trks and were evaluated and representative compounds were listed as examples. Results/conclusion: Several series of Trk inhibitors with excellent in vitro potencies have been reported and a number of compounds have gone into the clinic. It should be noted that few of these inhibitors are Trk selective, demonstrating that targeting Trk kinases for treatment of pain and/or cancer offers a promising but also challenging approach.     

神经营养因子的两类受体:Trks及p75(综述)

此文简要回顾了神经营养因子的两类受体——酪氨酸激酶受体家族 (Trks)及 p75的分子结构、分布、相互作用 ,与神经营养因子的结合及其后的信号传导路径     

神经营养素受体在幼年大鼠神经系统表达的特点

为了研究神经营养素受体 ( Trks)在幼年大鼠神经系统的表达模式及分布规律。本研究应用免疫组织化学技术对幼年大鼠大脑皮质、小脑、脊髓、背根神经节中 Trks的表达及分布进行了形态学观察及定位。结果证明 ,神经营养素受体 Trk A,Trk B,Trk C在大脑皮质、脊髓、背根神经节中均有表达 ,Trk B呈强阳性且分布广 ,Trk A次之 ,Trk C为弱阳性 ;在小脑 Purkinje细胞Trk C表达阳性 ,Trk A弱阳性 ,Trk B阴性。结论 :幼年大鼠神经系统中 Trks表达存在差异 ,提示神经系统不同部位发育所需的神经营养素不同 ;Trks的分布部位与已报道的神经营养素的分布部位不完全重叠 ,可能与神经营养素作用模式多样性有关     

神经母细胞瘤中Trk基因的表达及临床意义

目的本研究通过检测不同分期神经母细胞瘤(NB)患儿中Trk基因家族的表达分布,了解Trk家族表型在不同分期的NB中表达的差异。方法收集2005年-2013年期间中山大学孙逸仙纪念医院儿童肿瘤专科确诊的12例NB患儿病理标本,全部病例取其病理标本切片4张,分别通过免疫组织化学方法检测TrkA、TrkB和Trk C的表达。结果本组NB病例共有Ⅱ期3例,Ⅳ期9例;Ⅱ期NB中有TrkA阳性2例(67%),TrkB阳性2例(67%),TrkC阳性2例(67%);Ⅳ期NB中有TrkA阳性3例(33%),TrkB阳性9例(100%),TrkC阳性2例(22%),分别比较Ⅱ期及Ⅳ期的TrkA、TrkB和Trk C阳性率,发现差异均无显著性(P0.05)。结论不同Trk基因在不同分期的NB中分布各异,TrkA及Trk C在预后较好的Ⅱ期NB中阳性率为67%,TrkB在预后较差的Ⅳ期NB中全部阳性,说明Trk基因家族的表达分布与NB的分期及预后有关。本组病例组间Trk基因分布无显著差异的原因可能与样本量过少有关。