Divergent metabolic responses dictate vulnerability to NAMPT inhibition in ovarian cancer
Divergent metabolic responses dictate vulnerability to NAMPT inhibition in ovarian cancer
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DOI：
10.1002/1873-3468.13736
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发表时间：
2020-01-26
期刊：
影响因子：
3.5
通讯作者：
Tanuma, Nobuhiro
中科院分区：
文献类型：
--
作者：
Kudo, Kei;Nomura, Miyuki;Tanuma, Nobuhiro
目前人们感兴趣的是针对癌症代谢作为许多恶性肿瘤的治疗方法，包括卵巢癌（OVC），其中几乎没有发现可药物驱动突变。烟酰胺磷酸核糖转移酶 (NAMPT) 是 NAD 挽救途径中的限速酶，是 OVC 的潜在治疗靶点。然而，决定 NAMPT 抑制反应的因素尚不完全清楚。在这里，我们报告 OVC 细胞系可以分为表现出 NAMPT 依赖性或 NAMPT 独立糖酵解的亚组，这些代谢差异与 NAMPT 抑制的脆弱性相关。有趣的是，表现出 NAMPT 依赖性糖酵解的细胞在一组缺乏 BRCA1/2 基因突变的细胞中富集。我们的研究结果表明，选择合适的 OVC 患者进行 NAMPT 靶向治疗的重要性。
It is of current interest to target cancer metabolism as treatment for many malignancies, including ovarian cancer (OVC), in which few druggable driver mutations have been identified. Nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting enzyme in the NAD salvage pathway, is a potential therapeutic target in OVC. However, factors that determine responsiveness to NAMPT inhibition are not fully understood. Here, we report that OVC cell lines can be divided into subgroups exhibiting NAMPT-dependent or NAMPT-independent glycolysis, and these metabolic differences correlate with vulnerability to NAMPT inhibition. Interestingly, cells showing NAMPT-dependent glycolysis were enriched in a group of cells lacking BRCA1/2 gene mutations. Our findings suggest the importance of selecting appropriate patients for NAMPT-targeting therapy in OVC.