在垂体神经内分泌瘤中,panobinostat针对Nrf2的治疗潜力
Yijun Cheng1, Yuting Dai2, Hao Tang1
1Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197# Ruijin er road, Shanghai, 200025, China.
Acta neuropathologica communications
|April 18, 2024
概括
激素脱乙酶抑制剂 (HDACIs),特别是帕诺比诺斯塔特,显示出希望作为有效的药物疗法用于垂体瘤 (PitNETs). 将Panobinostat与Nrf2抑制剂结合使用,通过调节Nrf2信号来协同增强其抗PitNET作用.
科学领域:
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
- 基因组学就是基因组学.
背景情况:
- 下垂体瘤 (PitNETs) 是一个重要的临床挑战,目标治疗有限.
- 识别细胞内在的脆弱性对于开发有效的PitNET治疗至关重要.
研究的目的:
- 在PitNET中识别可用药物的细胞内在漏洞.
- 通过高通量查和基因组分析,为PitNET发现新的基于目标的药物疗法.
主要方法:
- 高通量药物查 (HTS) 对9个来自患者的PitNET初级细胞.
- 180个PitNET样本的基因组测序,以确定潜在的药物标.
- 鉴定药物候选物的体外,体内和初级细胞模型验证,包括RNA测序以阐明机制.
主要成果:
- HTS确定了针对瘤性途径的多种药物类别,其中HDAC抑制剂 (HDACIs) 显示出最高的强度.
- 作为HDACI的代表药物,帕诺宾诺斯塔特在临床前的PitNET模型中显示出显著的疗效.
- 帕诺比诺斯塔特治疗改变了Nrf2信号传递,在PitNET中高度表达;与Nrf2抑制剂 (ML385) 联合治疗显示出协同作用的抗PitNET效应.
结论:
- HDAC 抑制剂代表了用于PitNET治疗的一类有前途的药物.
- 帕诺比诺斯塔特是PitNETs的潜在治疗剂,通过Nrf2-介导的氧化还原调制起作用.
- 与Panobinostat和ML385的联合治疗为PitNET治疗提供了增强的疗效.
相关概念视频
NF-κB-dependent Signaling Pathway
7.4K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.4K
Targeted Cancer Therapies
7.6K
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...
7.6K
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
Transducer Mechanism: Nuclear Receptors
1.3K
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
1.3K
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
The Nucleolus
8.8K
The nucleolus is the most prominent substructure of the nucleus. When it was first discovered, it was considered to be an isolated organelle that forms fibrils and granules. In 1931, the relationship between the nucleolus and chromosomes was first described by Heitz. He observed that the appearance and size of nucleolus varies depending on the stage of the cell cycle. He also noticed constricted regions on different chromosomes clustered together at definite cell cycle stages. These regions,...
8.8K


