朱蒙吉基因素脱甲基酶是小细胞肺癌的治疗点
Aiden Nguyen1, Clarissa G Nuñez1, Tram Anh Tran1
1Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas, TX, USA.
Oncogene
|August 17, 2024
概括
朱蒙吉脱甲基酶抑制剂显示出对小细胞肺癌 (SCLC) 的承诺. 这些抑制剂针对SCLC的脆弱性,诱导细胞死亡和阻断瘤生长,提供了一种新的治疗途径.
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:
- 小细胞肺癌 (SCLC) 是一种神经内分泌癌症,治疗进展有限.
- 针对特定的弱点是开发新型SCLC治疗的关键.
研究的目的:
- 识别和验证SCLC的治疗漏洞.
- 调查Jumonji氨酸脱甲基酶 (KDM) 抑制剂作为新型SCLC治疗的潜力.
主要方法:
- 使用了临床前的SCLC模型,包括耐埃托胺细胞系和瘤异种移植.
- 使用针对Jumonji KDMs的小分子抑制剂 (泛抑制剂JIB-04,KDM4抑制剂SD70).
- 评估了对细胞增殖,细胞内网膜 (ER) 应激,细胞死亡和SCLC特异性蛋白质标记物的影响.
主要成果:
- Jumonji KDM 抑制剂在体外和体内有效地阻止了SCLC恶性生长.
- 耐乙胺SCLC细胞系对Jumonji抑制表现出特别的敏感性.
- 抑制Jumonji KDMs诱导了ER压力,触发了亡,并降低了SCLC的神经内分泌标记物和驱动转录因子.
结论:
- 朱蒙吉KDM抑制剂代表了SCLC的一个有前途的治疗策略.
- KDM4A被确定为SCLC的相关点,调节ER压力和扩散.
- 这些发现支持Jumonji KDM抑制剂用于SCLC治疗的临床评估.
相关概念视频
Targeted Cancer Therapies
7.5K
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...
7.5K
Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
Histone Modification
13.2K
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
13.2K
Cancer-Critical Genes II: Tumor Suppressor Genes
7.3K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
7.3K
Eukaryotic Transcription Inhibitors
9.8K
Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
9.8K
Tumor Immunotherapy
493
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.
493


