恶性胶质瘤靶向治疗研究进展

目的 恶性胶质瘤是一种最常见的原发恶性脑肿瘤,是癌症治疗中最具挑战性疾病之一.因为手术切除后肿瘤易复发和治疗抵抗性,患者预后普遍较差.胶质瘤的分子靶向治疗正逐渐引起广泛关注.本研究总结恶性胶质瘤发病相关的分子病理改变和靶向药物的临床应用与研究进展.方法 采用PubMed文献检索系统,以“恶性胶质瘤”和“分子靶向治疗”为关键词,检索2007-01-01-2015-12-31的相关文献.纳入标准:(1)与恶性胶质瘤分子靶向通路相关的文献;(2)与恶性胶质瘤抗血管生成治疗相关的文献;(3)与恶性胶质瘤分子靶向药物的Ⅰ期及Ⅱ期临床研究相关的文献;(4)与恶性胶质瘤分子靶向耐药相关的文献.根据纳入标准分析文献43篇.结果 胶质瘤靶向治疗方向主要集中在RTK/RAS/PI3K通路、促血管生成通路和一些其他重要的细胞内信号转导通路.然而,一些因素如信号通路之间的串扰、瘤内异质性和胶质瘤干细胞的治疗抵抗性限制了单一药物的活性.各种分子靶向药物单药治疗未能表现出更好的生存获益,还需与其他治疗方法联合应用.目前对于恶性胶质瘤患者多靶点激酶抑制剂治疗的研究还处于起始阶段.结论 分子靶向药物在恶性胶质瘤的治疗中具有重要临床意义和应用潜力,但由于胶质瘤的复杂的分子生物学特性,分子靶向治疗面临诸多挑战,还需进一步探索与研究.

Research progress of targeted therapy for malignant glioma

OBJECTIVE Malignant gliomas are the most common primary malignant brain tumors,which are the most challenging diseases in the treatment of cancer.Despite the progress of the traditional treatment,the prognosis of the patients is generally poor.This is because tumor recurrence after surgical removal and treatment resistant.In the past ten years,the molecular targeted therapy of gliomas has gradually attracted people's attention.In this paper,we summarize the molecular pathological changes in the pathogenesis of malignant gliomas and clinical application and research advances of targeted agents.METHODS Publications from 2007 to 2015 on the study of clinical application and research advances of targeted agents were searched by the key words of "malignant gliomas,molecular targeted therapy" from publication databases such as PubMed.Forty-three articles were collected in accordance with the inclusion criterion.Inclusion criterion:molecular targeting pathway of malignant gliomas;anti-angiogenesis therapy of malignant gliomas;phase Ⅰ / Ⅱ trials of molecular targeted agents;and resistance of molecular targeted agents.RESULTS The direction of glioma treatment is mainly focused on the receptor tyrosine kinase/RAS/phosphatidylinositol 3-kinase pathway,proangiogenic pathways and some other important intracellular signal transduction pathways.Some factors such as signal pathway between crosstalk,intratumoral heterogeneity and glioma stem cell treatment resistant limited the activity of single agents.Various molecular targeted agents monotherapy failed to show a better survival benefit,they need to be combined with other treatment methods.At present,the research of multi-target therapy in patients with malignant glioma is still in the initial stage.CONCLUSIONS Molecular targeted agents play critical roles and present a bright potential in the treatment of malignant glioma.However,due to the complex molecular biological characteristics of the glioma,molecular targeted therapy is facing many challenges and needs further exploration and research.