文章：

癌症中的营养清除

Nutrient scavenging in cancer

原文发布日期：2018-08-10

DOI: 10.1038/s41568-018-0048-x

类型: Review Article

开放获取: 否

英文摘要：

While cancer cell proliferation depends on access to extracellular nutrients, inadequate tumour perfusion means that glucose, amino acids and lipids are often in short supply. To overcome this obstacle to growth, cancer cells utilize multiple scavenging strategies, obtaining macromolecules from the microenvironment and breaking them down in the lysosome to produce substrates for ATP generation and anabolism. Recent studies have revealed four scavenging pathways that support cancer cell proliferation in low-nutrient environments: scavenging of extracellular matrix proteins via integrins, receptor-mediated albumin uptake and catabolism, macropinocytic consumption of multiple components of the tumour microenvironment and the engulfment and degradation of entire live cells via entosis. New evidence suggests that blocking these pathways alone or in combination could provide substantial benefits to patients with incurable solid tumours. Both US Food and Drug Administration (FDA)-approved drugs and several agents in preclinical or clinical development shut down individual or multiple scavenging pathways. These therapies may increase the extent and durability of tumour growth inhibition and/or prevent the development of resistance when used in combination with existing treatments. This Review summarizes the evidence suggesting that scavenging pathways drive tumour growth, highlights recent advances that define the oncogenic signal transduction pathways that regulate scavenging and considers the benefits and detriments of therapeutic strategies targeting scavenging that are currently under development.

摘要翻译： 

虽然癌细胞的增殖依赖于细胞外营养物质的获取，但肿瘤灌注不足常导致葡萄糖、氨基酸和脂质供应短缺。为突破这一生长障碍，癌细胞采用多种清除策略：从微环境中获取大分子，并通过溶酶体分解产生ATP生成和合成代谢所需的底物。近期研究揭示了在低营养环境中支持癌细胞增殖的四条清除途径：通过整合素清除细胞外基质蛋白、受体介导的白蛋白摄取与分解代谢、对肿瘤微环境中多种成分的大胞饮作用，以及通过内噬作用对整个活细胞的吞噬降解。新证据表明，单独或联合阻断这些途径可为不可治愈的实体瘤患者带来显著获益。目前已有美国食品药品监督管理局批准药物及多个临床前或临床开发中的制剂可阻断单条或多条清除途径。这些疗法与现有治疗手段联用时，可增强肿瘤生长抑制的深度与持久性，并预防耐药性产生。本综述总结了清除途径驱动肿瘤生长的证据，重点阐述了界定调控清除过程的致癌信号转导通路的最新进展，并评估了目前正在开发中的靶向清除治疗策略的利弊。

原文链接：

Nutrient scavenging in cancer