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与NAMPT抑制一起的氨酸限制对神经内分泌癌的合成致死性

Miyuki Nomura¹, Mai Ohuchi¹, Yoshimi Sakamoto¹

¹Division of Cancer Chemotherapy, Miyagi Cancer Center Research Institute, Natori, Japan.

Nature communications

|December 13, 2023

概括

神经内分泌癌细胞易受尼古丁胺酸基转移酶抑制剂 (NAMPTi) 的影响. 饮食变化通过向尼古丁酸 рибо (NAR) 代谢来增强NAMPTi的疗效,改善癌症治疗策略.

科学领域:

在瘤学瘤学.
生物化学生物化学
代谢途径代谢途径

背景情况:

尼古丁胺胺酸基转移酶 (NAMPT) 对于NAD+生物合成和癌症点至关重要.
目前尚不完全了解NAMPT抑制剂 (NAMPTi) 的疗效.
神经内分泌分化影响癌细胞代谢和药物反应.

研究的目的:

确定预测癌症易受NAMPT抑制剂影响的因素.
研究神经内分泌表现型在NAMPTi疗效中的作用.
探索饮食修改以增强NAMPTi治疗.

主要方法:

在神经内分泌癌细胞的体外研究.
对NAD+生物合成途径的分析 (de novo和救援).
鼠标移植模型,以评估治疗疗效和代谢干预措施.

主要成果:

神经内分泌表型预测肺癌和前列腺癌中对NAMPT抑制剂的敏感性.
神经内分泌的分化降低了新的NAD+合成的调节,增加了NAMPTi的敏感性.
循环的尼古丁酸 рибоoside (NAR) 通过支持NAMPT独立的NAD+合成来对抗NAMPTi.
营养或遗传性NAR枯竭与NAMPTi协同作用,导致瘤中的合成致死性.

结论:

神经内分泌的分化是NAMPTi疗效的关键决定因素.
与NAMPT一起准NAR代谢,为神经内分泌癌症提供了一种新的治疗策略.
对NAR的饮食和遗传干预可以加强NAMPT抑制剂治疗.

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