相关实验视频

Updated: Sep 9, 2025

Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures

Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures

Published on: December 26, 2016

在三阴性乳腺癌中,CerS2是可用药物的标

Hissah Alatawi, Haritha H Nair, Lingbao Ai

bioRxiv : the preprint server for biology

|September 2, 2025

概括

一种新的药物DH20931激活胺合成酶2 (CerS2),诱导三阴性乳腺癌的细胞死亡. 这种新疗法针对ER压力和线粒体过载,显示出显著的临床前疗效.

科学领域:

生物化学
分子生物学
癌症学

背景情况:

由于其侵袭性和有限的向治疗选择,三阴性乳腺癌 (TNBC) 存在重大治疗挑战.
胺合成酶2 (CerS2) 是一种合成亲细胞灭绝性非常长链胺的酶,是TNBC的潜在治疗点.

研究的目的:

鉴定和描述DH20931,一种新的小分子CerS2激动剂.
阐明DH20931在乳腺癌细胞中诱导亡的机制.
评估DH20931对TNBC的临床前疗效和安全性.

主要方法:

在体外生化测试以评估CerS2激活和VLCC合成.
基于细胞的测试以测量ER压力,细胞亡信号 (ATF4/CHOP/PUMA) 和流量.
在体内研究,使用TNBC细胞系在正位体和患者衍生的异种移植模型中.

主要成果:

在乳腺癌细胞中增加VLCC水平.
DH20931通过ATF4/CHOP/PUMA途径诱导ER压力和亡.
DH20931促进了CerS2和IP3R1之间的新相互作用,导致线粒体过载和亡.
在临床前模型中,DH20931表现出强烈的TNBC生长抑制,具有良好的安全性.

结论:

在TNBC治疗中,CerS2是可用药物的标.
通过诱导脂毒性,ER压力和线粒体过载,DH20931代表了TNBC的第一类治疗策略.
针对CerS2提供了一种对抗侵袭性乳腺癌的新方法.

更多相关视频

Quantifying Antibody-Dependent Cellular Cytotoxicity in a Tumor Spheroid Model: Application for Drug Discovery

Quantifying Antibody-Dependent Cellular Cytotoxicity in a Tumor Spheroid Model: Application for Drug Discovery

Published on: April 26, 2024

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells

Published on: August 12, 2015

相关概念视频

Targeted Cancer Therapies

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...

Inhibition of Cdk Activity

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...

Treatment Resistant Cancers

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...