Neurofibromatosis type 1 (Nf1) is a neurodevelopmental disorder and tumor syndrome caused by loss of function mutations in the neurofibromin gene (Nf1) and is estimated to affect 100,000 people in the US. Behavioral alterations and cognitive deficits have been found in 50–70% of children with Nf1 and include specific problems with attention, visual perception, language, learning, attention, and executive function. These behavioral alterations and cognitive deficits are observed in the absence of tumors or macroscopic structural abnormalities in the central nervous system. No effective treatments for the behavioral and cognitive disabilities of Nf1 exist. Inhibition of the anaplastic lymphoma kinase (Alk), a kinase which is negatively regulated by neurofibromin, allows for testing the hypothesis that this inhibition may be therapeutically beneficial in Nf1. In this review, we discuss this area of research and directions for the development of alternative therapeutic strategies to inhibit Alk. Even if the incidence of adverse reactions of currently available Alk inhibitors was reduced to half the dose, we anticipate that a long-term treatment would pose challenges for efficacy, safety, and tolerability. Therefore, future efforts are warranted to investigate alternative, potentially less toxic and more specific strategies to inhibit Alk function.
1型神经纤维瘤病（Nf1）是一种由神经纤维蛋白基因（Nf1）功能缺失突变引起的神经发育障碍与肿瘤综合征，据估计在美国影响约10万人。50-70%的Nf1患儿存在行为改变与认知缺陷，具体表现为注意力、视觉感知、语言能力、学习能力及执行功能等方面的特定问题。这些行为与认知障碍的出现并不伴随中枢神经系统肿瘤或宏观结构异常。目前针对Nf1行为与认知障碍尚无有效治疗方法。间变性淋巴瘤激酶（Alk）作为受神经纤维蛋白负向调控的激酶，其抑制为验证“该抑制可能对Nf1产生治疗效益”的假说提供了可能。本文综述该领域研究进展，并探讨开发替代性Alk抑制治疗策略的方向。即使现有Alk抑制剂的不良反应发生率降至半剂量水平，我们预计长期治疗仍将在疗效、安全性和耐受性方面面临挑战。因此，有必要进一步探索替代性、潜在毒性更低且更具特异性的Alk功能抑制策略。
肿瘤(癌症)患者之家