在癌症中针对TP53无意义突变的治疗向
Charlotte Strandgren1, Klas G Wiman1
1Karolinska Institutet, Departement of Oncology-Pathology, Stockholm, Sweden.
Upsala journal of medical sciences
|June 12, 2024
概括
在TP53瘤抑制基因中的无意义突变可以作为癌症治疗的目标. 诱导转化读透可以恢复全长的p53蛋白,可能导致瘤细胞死亡.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 在人类癌症中,TP53瘤抑制基因突变很常见.
- 大约10%的TP53突变是无意义的突变,导致截断的,不活跃的p53蛋白.
研究的目的:
- 研究诱导转化读透的潜力,以恢复具有TP53无意义突变的瘤中的功能性p53蛋白.
- 通过阅读诱导恢复p53功能的治疗影响.
主要方法:
- 利用氨基甘油酸抗生素和新型化合物来诱导翻译阅读.
- 评估了具有TP53无意义突变的瘤细胞中全长p53蛋白的产生.
- 评估了读透诱导的p53的功能能力,以对目标基因进行交换激活,并诱导瘤细胞死亡.
主要成果:
- 在具有各种TP53无意义突变的瘤细胞中成功诱导了全长的p53蛋白.
- 生成的全长p53蛋白保留了它对p53点基因进行交换活化的能力.
- 读透诱导的p53触发了瘤细胞死亡,表明恢复了瘤抑制功能.
结论:
- 翻译阅读是一种可行的策略,可以抵消TP53无意义突变的影响.
- 这种方法对开发新型疗法具有前途,用于含有TP53无意义突变的人类癌症的显著子集.
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
Cancer-Critical Genes II: Tumor Suppressor Genes
7.4K
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...
7.4K
Loss of Tumor Suppressor Gene Functions
4.8K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
4.8K
Tumor Immunotherapy
514
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.
514
mTOR Signaling and Cancer Progression
3.8K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.8K


