抑制真核生物发起因子eIF4E克服了胃癌中的阿贝马西克利布抵抗
Huo-Long Zha1, Wei Chen2, Wei Shi3
1Department of Gastroenterology, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, China.
Current medical science
|September 26, 2023
概括
使用利巴维林向真核转化启动因子4E (eIF4E) 克服了胃癌中abemaciclib的耐药性. 这种组合疗法通过抑制eIF4E和抑制瘤生长而无毒性的治疗晚期胃癌具有前途.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症治疗方法 癌症治疗方法
背景情况:
- 异常的环素依赖性激酶4和6 (CDK4/6) 突变在胃食道癌中很普遍.
- 像abemaciclib这样的CDK4/6抑制剂在这些瘤的单一治疗中显示出有限的疗效.
- 了解abemaciclib耐药机制对于改善治疗结果至关重要.
研究的目的:
- 调查胃癌中abemaciclib耐药性的基础机制.
- 评估向真核转化启动因子4E (eIF4E) 克服这种抵抗的治疗潜力.
- 评估将abemaciclib与eIF4E抑制剂利巴维林结合使用的疗效.
主要方法:
- 产生了抗abemaciclib的胃癌细胞系.
- 评估了-真核转化启动因子4E (p-eIF4E) 和eIF4E的表达.
- 利用siRNA倒置来分析eIF4E在抵抗中的作用.
- 在胃癌异种移植模型中评估了利巴维林和abemaciclib联合治疗.
主要成果:
- 在抵抗abemaciclib.lib的胃癌细胞中观察到eIF4E的升级.
- 增加的eIF4E水平与加强对eIF4E抑制的反应相关,特别是在耐药细胞中.
- 里巴维林通过抑制eIF4E在体外和体内显著增强了abemaciclib的疗效.
- 利巴维林在小鼠中有效抑制了对abemaciclib耐药胃癌的生长,没有观察到毒性.
结论:
- 针对eIF4E是一种可行的策略,可以提高abemaciclib在胃癌治疗的疗效.
- 结合CDK4/6抑制剂和利巴维林的联合治疗有可能治疗晚期胃癌.
- 这种方法为克服胃食道恶性瘤中的abemaciclib耐药性提供了一个有希望的策略.
相关概念视频
02:34Inhibition of Cdk Activity
4.8K
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...
4.8K
02:38Mitogens and the Cell Cycle
6.5K
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...
6.5K
02:57Targeted Cancer Therapies
7.7K
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...
There are several types of targeted therapies against...
7.7K
02:56Treatment Resistant Cancers
3.3K
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...
3.3K
02:50Combination Therapies and Personalized Medicine
4.9K
Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
4.9K