激酶抑制剂GNF-7在Topoisomerase 1-deficientEwing肉瘤中是合成致命的
相关实验视频
Updated: May 31, 2026

12:03
In Vivo Model for Testing Effect of Hypoxia on Tumor Metastasis
Published on: December 9, 2016
12.5K
Carly M Sayers1, Morgan B Carter1, Haiyan Lei1
1Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Cancers
|August 14, 2025
概括
一个新的分子,GNF-7,通过准TOP1缺乏细胞,显示出对治疗尤文肉瘤 (ES) 的希望. 这一发现为复发性或耐药性ES患者提供了希望,特别是当与现有疗法相结合时.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 药物发现 药物发现 药物发现
背景情况:
- 尤文肉瘤 (ES) 是一种由EWS::FLI1coprotein驱动的侵袭性儿科癌症.
- 目前对转移性或复发性ES的治疗方法长期有效性有限.
- 拓酶1 (TOP1) 抑制剂是复发性ES的标准疗法.
研究的目的:
- 确定ES中对TOP1抑制剂的耐药性机制.
- 发现对ES有效的新型小分子,特别是在耐药环境中.
主要方法:
- 全基因组的CRISPR淘汰图书馆屏幕,以确定TOP1删除作为抵抗机制.
- 使用同位素细胞系的高通量小分子屏幕.
- 描述GNF-7的分子标和活动.
主要成果:
- 删除TOP1会对TOP1抑制剂产生抗性.
- 在缺少TOP1的ES细胞中,GNF-7表现出明显更高的功效.
- GNF-7 抑制关键激酶 (CSK,p38α,EphA2,Lyn,ZAK) 并降低 EWS::FLI1 诱导基因的调节.
结论:
- GNF-7是ES的潜在治疗剂,特别是在TOP1耐药病例中.
- 具有相似的激酶配置文件的小分子可能会克服TOP1抑制剂耐药性.
- 与GNF-7和TOP1抑制剂的联合治疗需要进一步研究ES治疗.
相关概念视频
In-vitro Mutagenesis
To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
Mitogens and the Cell Cycle
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
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 specific...
There are several types of targeted therapies against specific...
Inhibitors of Bacterial DNA Synthesis
Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases—DNA gyrase and topoisomerase IV—are critical to this process, as they resolve DNA supercoiling and unlink chromosomes during replication. Fluoroquinolones, synthetic derivatives of quinolones, exploit this mechanism by stabilizing the transient DNA–enzyme cleavage complex, preventing strand religation, and causing lethal double-strand breaks. These antibiotics are selectively...

