眼内恶性肿瘤基因靶向治疗研究进展

Advances in gene targeted therapy for intraocular malignant tumors

随着精准医学的发展,靶向治疗作为一种新型生物治疗手段,越来越成为研究的热点。本文就葡萄膜恶性黑色素瘤(uveal malignant melanoma,UM)、视网膜母细胞瘤(retinoblastoma,RB)和原发性玻璃体视网膜淋巴瘤(primary vitreoretinal lymphoma,PVRL)基因靶向治疗的研究进展进行综述。针对UM患者,GNAQ/GNA11基因的突变率超过90%,GαQ和Gα11蛋白抑制剂FR900359或其衍生物可能是一种潜在的治疗选择。蛋白激酶C和ERK激酶抑制剂联合治疗可能改善转移性UM患者的治疗反应。针对Yes相关蛋白的靶向治疗策略可能是未来治疗UM的有效手段。Nutlin-3a是MDM2-p53相互作用的小分子抑制剂,它在高浓度时可杀死视网膜母细胞株。SYK抑制剂是开发中的RB治疗潜在靶点。沉默CKS1B基因可以抑制RB细胞的生长和侵袭。伊布替尼可能预防或延迟CD79B阳性PVRL患者中枢神经系统受累。

With the development of precision medicine,targeted therapy,as a new biologic therapy,has become a hot research topic.This paper reviewed the advances in gene targeted therapy for uveal malignant melanoma(UM),retinoblastoma(RB)and primary vitreoretinal lymphoma(PVRL).With the mutation rate of GNAQ/GNA11 gene exceeding 90%in UM patients,GαQ and Gα11 protein inhibitors FR900359 or their derivatives may be a potential therapeutic option.Combination therapy with protein kinase C and ERK kinase inhibitors may improve the treatment response in patients with metastatic UM.Targeted therapy strategies for Yes associated protein may be an effective means to treat UM in the future.Nutlin-3a is a small molecular inhibitor of MDM2-p53 interaction,which kills retinal mother cell lines at high concentrations.SYK inhibitors are potential targets for RB treatment under development.Silencing CKS1B gene can inhibit the growth and invasion of RB cells.Ibrutinib may prevent or delay central nervous system involvement in CD79B-positive PVRL patients.