准ABCD1-ACOX1-MET/IGF1R轴可以抑制多发性骨髓瘤
Zhannan Han1, Zhibo Yan1, Zhehan Ma2
1Department of Pathology, Duke University School of Medicine, Durham, NC, 27710, USA.
Leukemia
|January 30, 2025
概括
非常长链脂肪酸 (VLCFA) 影响多发性骨髓瘤 (MM) 治疗的有效性. 抑制VLCFA降解可以增强化疗,并向关键信号通路,为这种无法治愈的癌症提供新的治疗策略.
科学领域:
- 血液学 血液学 血液学
- 癌症生物学 癌症生物学
- 代谢途径 代谢途径
背景情况:
- 多发性骨髓瘤 (MM) 是一种无法治愈的血液癌症,需要新的治疗方法.
- 细胞内非常长链脂肪酸 (VLCFA) 与MM细胞存活和耐药性有关.
研究的目的:
- 研究VLCFA代谢在调节多发性骨髓瘤化疗药物的疗效中的作用.
- 通过了解VLCFA水平与MM细胞信号传递之间的联系,识别新的治疗点.
主要方法:
- 评估抑制VLCFA生物合成和降解对MM细胞死亡的影响.
- 在MM异种移植模型中评估ACOX1抑制剂与博尔特佐米布的协同效应.
- 分析改变VLCFA水平对MET和IGF1R激酶活性和信号的影响.
主要成果:
- 抑制VLCFA生物合成降低了博特佐米布诱导的细胞死亡.
- 通过ACOX1抑制抑制VLCFA降解,增强了博尔特佐米布,卡菲尔佐米布和莱纳利多米德的细胞毒性.
- 抑制ACOX1与博特佐米布合作,抑制了耐药MM异种移植的生长,降低了MET和IGF1R活性,并改变了酶-脑胺相互作用.
结论:
- MM细胞具有与VLCFA水平相关的代谢脆弱性.
- 准VLCFA代谢轴,特别是ACOX1,是多发性骨髓瘤的一种有前途的治疗策略.
- 调节VLCFA水平可以通过影响MET和IGF1R信号来克服对现有的MM疗法的抵抗.
更多相关视频
05:32Multimodal Bioluminescent and Positronic-emission Tomography/Computational Tomography Imaging of Multiple Myeloma Bone Marrow Xenografts in NOG Mice
Published on: January 7, 2019
6.8K
07:24Repression of Multiple Myeloma Cell Growth In Vivo by Single-wall Carbon Nanotube SWCNT-delivered MALAT1 Antisense Oligos
Published on: December 13, 2018
6.4K
相关概念视频
Targeted Cancer Therapies
7.4K
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...
7.4K
Abnormal Proliferation
4.4K
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...
4.4K
Combination Therapies and Personalized Medicine
4.8K
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...
4.8K
Inhibition of Cdk Activity
4.6K
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...
4.6K
Mitogens and the Cell Cycle
6.4K
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...
6.4K
