恶性肿瘤脑膜转移发生机制及治疗研究进展

Research Progress on the Mechanism of Occurrence and Treatment of Leptomeningeal Metastasis of Malignant Tumors

摘要: 脑膜转移(Leptomeningeal metastasis, LM)是多种恶性肿瘤相对罕见却最严重最具挑战性的并发症，致死率极高。通常癌细胞可通过直接侵犯、血行播散、神经内、神经轴位及血管周围扩散、淋巴系统转移等途径浸润脑膜进入脑脊液(Cerebrospinal fluid, CSF)。CSF微环境处于缺氧及无细胞状态，仅含少量中间代谢产物及微量元素，癌细胞进入CSF后需要克服CSF微环境的限制并且躲避免疫反应。也有学者发现LM患者的CSF中补体C3 (Complement Component 3, C3)升高，可进一步提高血脑屏障通透性。对CSF中ctDNA进行检测可帮助了解肿瘤的基因突变特征、LM的发生发展机制及确定新的治疗靶点。目前LM转移的治疗方法有：鞘内化疗、放射治疗、靶向治疗及免疫治疗。通过对其机制的研究，后续针对LM治疗方案的制定是十分有益的。本文主要针对LM可能的发生机制及目前最新的相关治疗进展进行综述。

Abstract: Leptomeningeal metastasis (LM) is a relatively rare but the most serious and challenging complication of many malignant tumors, with an extremely high lethality rate. Cancer cells usually enter the CSF by infiltrating the leptomeninges through direct invasion, hematogenous dissemination, intra-neural, neuraxial and perivascular spread, and lymphatic metastasis, etc. The microenvironment of the CSF is hypoxic and acellular, and contains only a small amount of intermediary metabolites and micronutrients, so that the cancer cells need to overcome the limitations of the CSF microenvironment and avoid immune responses after entering the CSF. Some scholars have also found that C3 is elevated in the CSF of LM patients, which can further increase the permeability of the blood-brain barrier. Detection of ctDNA in CSF can help to understand the gene mutation characteristics of the tumor, the mechanism of LM development and identify new therapeutic targets. Current treatments for LM metastasis include intrathecal chemotherapy, radiation therapy, targeted therapy and immunotherapy. The subsequent development of therapeutic regimens for LM is beneficial through the study of its mechanisms. In this article, we summarize the possible mechanisms of LM and the latest therapeutic advances.