时间标签：数据日期 2026-11-05 · 生成时间 2026-11-05 05:30（Asia/Shanghai）｜ 检索窗口 PubMed edat 2026/11/02 – 2026/11/06 ｜ 情报发生日期 2026-11-05
研究问题
We further sought to determine whether this screen-identified vulnerability could be supported by pharmacodynamic and efficacy studies in in vivo orthotopic NB models.Herein, we demonstrate a potent class effect of NAMPTis as effective agents against NB models.；Given the rarity of these entities and the dearth of novel therapies available for many pediatric malignancies, we sought to determine whether other pediatric solid tumors of unmet need might exhibit equivalent sensitivity to NAMPTis.；Using longitudinal live-cell image analysis, we tested the effects of three NAMPTis: first-generation clinical molecule daporinad and two second-generation clinical molecules OT-82 and KPT-9274 (Fig. 1B; Supplemental Fig.
方法
As pediatric cancers represent a group of cancers of high unmet clinical need, we sought to investigate if other pediatric solid tumors exhibit similarly high sensitivity to NAMPTis.；Using an unbiased high-throughput cancer cell line screen of over 200 cell lines, we identified that neuroblastoma (NB) is one of the most NAMPTi-sensitive solid tumor types, with sensitivity comparable or greater than that observed in pediatric sarcoma models.；Despite intense multimodal therapy, the prognosis for patients with high-risk NB is poor with an overall survival rate of less than 50% [25–27].
核心结论
We further sought to determine whether this screen-identified vulnerability could be supported by pharmacodynamic and efficacy studies in in vivo orthotopic NB models.Herein, we demonstrate a potent class effect of NAMPTis as effective agents against NB models.；Together, these findings establish NB as a clinically actionable indication for NAMPT inhibition and provide strong preclinical rationale for clinical study of NAMPTis in this disease.Materials and methodsKey reagents, including cell lines, compounds, antibodies, and commercial assays are detailed in Supplemental Table S1.；Although NAPRT expression does not preclude sensitivity to NAMPTis, this finding may suggest that NAPRT deficiency contributes to a differential in NAMPTi sensitivity between NAPRT expressing and non-expressing NB cell lines.
局限
However, double staining with PI and Annexin V was only observed in one cell line and occurred 24 h after the induction of PI staining alone, suggesting that OT-82 treatment results in a non-apoptotic mechanism of cell death (Fig. 5B; Supplemental Fig.；However, this occurred between 48 and 72 h of OT-82 treatment, suggesting that OT-82 is unlikely to be a primary autophagy inducer but rather that initiation of autophagy is a secondary or compensatory cellular response to NAD+ depletion in NB cells.；However, future clinical investigation of NAMPTis in NB should include correlative biology studies to better understand the potential relationship between NAPRT status and NAMPTi response in this malignancy.Alternatively, the downstream cell-type specific demands for NAD+ may contribute to NB dependency on NAMPT.
对本项目的价值
中高价值：属「干细胞 / 部分重编程与再生」方向；干细胞 / 再生 / 重编程栏目可用作本项目文献库与综述素材。 ｜ 价值分 3.0/5（★★★☆☆）
全文来源
PubMed PMC JATS（正文 55,731 字符，题名指纹 0.88，已过 PubMed PMCID 官方关联 + 题名指纹 + 正文长度归属校验）
原文题录
- 中文题名：治疗性 NAMPT 抑制揭示神经母细胞瘤可靶向的代谢脆弱性
- 英文标题：Therapeutic NAMPT inhibition reveals a targetable metabolic vulnerability in neuroblastoma.
- 期刊与标识：Journal of experimental & clinical cancer research : CR · PMID 42968146 · DOI 10.1186/s13046-026-03793-5 · PMC PMC13726087