Cheng Yan-Jie, Fan Fan, Zhang Zhong, Zhang Hai-Jun
Department of Oncology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, People's Republic of China.
Department of Oncology, Shanghai Fengxian District Central Hospital, Shanghai, China.
Expert Opin Ther Targets. 2023 Jul-Dec;27(9):861-878. doi: 10.1080/14728222.2023.2255377. Epub 2023 Sep 8.
Brain metastasis is a highly traumatic event in the progression of malignant tumors, often symbolizing higher mortality. Metabolic alterations are hallmarks of cancer, and the mask of lipid metabolic program rearrangement in cancer progression is gradually being unraveled.
In this work, we reviewed clinical and fundamental studies related to lipid expression and activity changes in brain metastases originating from lung, breast, and cutaneous melanomas, respectively. Novel roles of lipid metabolic reprogramming in the development of brain metastasis from malignant tumors were identified and its potential as a therapeutic target was evaluated. Published literature and clinical studies in databases consisting of PubMed, Embase, Scopus and www.ClinicalTrials.gov from 1990 to 2022 were searched.
Lipid metabolic reprogramming in brain metastasis is involved in de novo lipid synthesis within low lipid availability environments, regulation of lipid uptake and storage, metabolic interactions between brain tumors and the brain microenvironment, and membrane lipid remodeling, in addition to being a second messenger for signal transduction. Although some lipid metabolism modulators work efficiently in preclinical models, there is still a long way to go from laboratory to clinic. This area of research holds assurance for the organ-targeted treatment of brain metastases through drug-regulated metabolic targets and dietary interventions.
脑转移是恶性肿瘤进展过程中的一个极具创伤性的事件，通常预示着更高的死亡率。代谢改变是癌症的标志，癌症进展过程中脂质代谢程序重排的面纱正逐渐被揭开。
在这项工作中，我们分别回顾了与源自肺癌、乳腺癌和皮肤黑色素瘤的脑转移中脂质表达和活性变化相关的临床和基础研究。确定了脂质代谢重编程在恶性肿瘤脑转移发展中的新作用，并评估了其作为治疗靶点的潜力。检索了1990年至2022年期间PubMed、Embase、Scopus和www.ClinicalTrials.gov数据库中的已发表文献和临床研究。
脑转移中的脂质代谢重编程除了作为信号转导的第二信使外，还参与低脂质可用性环境中的从头脂质合成、脂质摄取和储存的调节、脑肿瘤与脑微环境之间的代谢相互作用以及膜脂质重塑。尽管一些脂质代谢调节剂在临床前模型中有效，但从实验室到临床仍有很长的路要走。这一研究领域有望通过药物调节代谢靶点和饮食干预实现脑转移的器官靶向治疗。
