向eIF4A触发了干扰素反应,与化疗协同作用,并抑制了三阴性乳腺癌

相关实验视频

Updated: Jul 12, 2025

08:47

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells

Published on: May 1, 2020

3.1K

Na Zhao¹, Elena B Kabotyanski¹, Alexander B Saltzman²

¹Department of Molecular and Cellular Biology.

The Journal of clinical investigation

|October 24, 2023

概括

Zotatifin 是一种eIF4A抑制剂,通过抑制瘤生长和重新编程免疫微环境来向三阴性乳腺癌 (TNBC). 它在与化疗和免疫疗法的联合疗法中显示出希望.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
免疫学免疫学免疫学

背景情况:

失调的蛋白质合成是癌症的标志,使mRNA转化抑制成为一个有前途的治疗策略.
三重阴性乳腺癌 (TNBC) 在有限的向疗法下构成了重大的临床挑战.

研究的目的:

研究一流的eIF4A抑制剂zototifin对TNBC及其免疫微环境的治疗作用.
阐明佐塔提芬作用的机制,并确定潜在的组合策略.

主要方法:

利用合成TNBC小鼠模型评估佐塔提芬对瘤细胞和免疫微环境的影响.
进行了机理学研究来分析翻译重编程,基因表达和细胞反应.
评估了与卡博普拉丁和免疫检查点封锁联合使用的佐塔提芬.

主要成果:

佐塔提芬抑制了瘤细胞的增殖,使巨细胞重新极化为类似M1的表型,并抑制了中性粒细胞的透.
从机制上讲,佐塔提芬重新编程了翻译场景,抑制了Sox4和Fgfr1的翻译,并诱导了均的干扰素 (IFN) 反应.
佐塔提芬与碳白金协同作用,诱导DNA损伤和IFN反应的增加,导致T细胞依赖的瘤抑制.
观察到IFN刺激的基因诱导患者活检后zotatifin治疗.

结论:

针对eIF4A使用佐塔提芬是TNBC的可行策略,影响瘤细胞和免疫微环境.
佐塔提芬显示出作为免疫检查点阻塞的敏感剂的潜力,并与化疗协同作用.
确定了潜在的药理动力学生物标志物,并为新型组合疗法建立了理由,其中包括用于TNBC治疗的佐他提芬.

关键词:

乳腺癌乳腺癌乳腺癌免疫治疗是一种免疫疗法.在瘤学瘤学.翻译翻译翻译翻译

相关概念视频

02:57

Targeted 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...

7.7K

02:50

Combination 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...

4.9K

01:27

Tumor Immunotherapy

538

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.

538

02:38

Mitogens 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

01:27

Combined Effects of Drugs: Synergism

4.0K

Synergism is a useful mechanism where combining two or more drugs is more effective than each constituent used alone. Such combinations are also called supra-additive interactions. The drugs collectively enhance the final therapeutic effect by acting on different targets. Another advantage is that the low dose of each constituent drug is sufficient to achieve the desired effect. This helps reduce the duration of therapy and lower the adverse effects of these drugs.
Such synergistic combinations...

4.0K

02:17

The Tumor Microenvironment

6.6K

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...