Ciminera Alexandra K, Jandial Rahul, Termini John
Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute, City of Hope, Duarte, CA, USA.
Department of Molecular Medicine, Beckman Research Institute, City of Hope, Duarte, CA, USA.
Clin Exp Metastasis. 2017 Oct;34(6-7):401-410. doi: 10.1007/s10585-017-9864-8. Epub 2017 Oct 23.
Metabolic adaptations permit tumor cells to metastasize to and thrive in the brain. Brain metastases continue to present clinical challenges due to rising incidence and resistance to current treatments. Therefore, elucidating altered metabolic pathways in brain metastases may provide new therapeutic targets for the treatment of aggressive disease. Due to the high demand for glucose in the brain, increased glycolytic activity is favored for energy production. Primary tumors that undergo Warburg-like metabolic reprogramming become suited to growth in the brain microenvironment. Indeed, elevated metabolism is a predictor of metastasis in many cancer subtypes. Specifically, metabolic alterations are seen in primary tumors that are associated with the formation of brain metastases, namely breast cancer, lung cancer, and melanoma. Because of this selective pressure, inhibitors of key metabolic factors may reduce tumor cell viability, thus exploiting metabolic pathways for cancer therapeutics. This review summarizes the metabolic advantages and vulnerabilities of brain metastases.
代谢适应使肿瘤细胞能够转移至脑部并在其中生长。由于发病率上升以及对当前治疗产生耐药性，脑转移瘤持续带来临床挑战。因此，阐明脑转移瘤中改变的代谢途径可能为侵袭性疾病的治疗提供新的治疗靶点。由于大脑对葡萄糖的需求量很高，增加糖酵解活性有利于能量产生。经历类似瓦伯格代谢重编程的原发性肿瘤变得适合在脑微环境中生长。事实上，代谢升高是许多癌症亚型转移的一个预测指标。具体而言，在与脑转移瘤形成相关的原发性肿瘤中，即乳腺癌、肺癌和黑色素瘤中，可见代谢改变。由于这种选择性压力，关键代谢因子的抑制剂可能会降低肿瘤细胞的活力，从而利用代谢途径进行癌症治疗。本综述总结了脑转移瘤的代谢优势和弱点。
