抗精神病药物通过破坏 lysosomal 功能和通过稳定 PTEN 抑制瘤信号来具有抗质母细胞瘤活性
John Ryan Jacob1, Kamalakannan Palanichamy2, Arnab Chakravarti1
1Department of Radiation Oncology, The Ohio State University College of Medicine and Comprehensive Cancer Center, Columbus, OH, 43210, USA.
Cell death & disease
|June 13, 2024
概括
重用中枢神经系统 (CNS) 药物对质母细胞瘤 (GBM) 治疗有希望. 这些药物破坏了 lysosomal 功能,导致 GBM 细胞死亡,特别是在 PTEN 完整的瘤中.
科学领域:
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
- 神经科学是一个神经科学.
背景情况:
- 质母细胞瘤 (GBM) 仍然是一个具有挑战性的脑癌,治疗选择有限.
- 重新利用已确定的安全性和血脑屏障透的药物,如中枢神经系统药物,是一种可行的治疗策略.
- 理解药物机制对于开发有效的癌症疗法至关重要.
研究的目的:
- 研究特定抗精神病药物和抗抑郁药的抗GBM疗效.
- 阐明这些重用药物在GBM中的作用机制.
- 确定影响GBM对这些药物敏感性的因素.
主要方法:
- 在体外和体外研究使用GBM模型进行.
- 评估了中枢神经系统药物对 lysosomal 功能和细胞活性的影响.
- 评估了与EGFR-PI3K-Akt途径抑制剂的协同效应.
主要成果:
- 抗精神病药物和抗抑郁药物通过破坏 lysosomal 功能,导致细胞死亡,表现出抗GBM活性.
- 无PTEN完整的GBM对这些化合物表现出高度敏感.
- lysosomal 功能和 EGFR-PI3K-Akt 途径的联合抑制导致显著的细胞崩.
结论:
- 重用中枢神经系统药物为GBM治疗提供了潜在的新治疗途径.
- 溶解体破坏是这些药物在GBM中细胞毒性的关键机制.
- 这些发现支持对中枢神经系统药物的进一步临床研究,用于治疗GBM和其他癌症.
更多相关视频
06:51Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
Published on: July 21, 2018
17.9K
08:46A Protocol for Rapid Post-mortem Cell Culture of Diffuse Intrinsic Pontine Glioma DIPG
Published on: March 7, 2017
16.9K
相关概念视频
01:10Drugs that Destabilize Microtubules
2.0K
Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
2.0K
01:15Drugs that Stabilize Microtubules
2.0K
Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.0K
02:57Targeted 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
01:29Chemotherapy-Induced Nausea and Vomiting: Dopamine Receptor Antagonists
257
Dopamine receptor antagonists, also known as antipsychotic agents, are critical in managing chemotherapy-induced vomiting. These antiemetic agents block dopamine receptors in the chemoreceptor trigger zone (CTZ), inhibiting signal transmission to the vomiting center. Antipsychotic agents encompass phenothiazines (PTZ), butyrophenones, benzamides, and thienobenzodiazepines (Zyprexa), which are utilized for their antiemetic and sedative properties.
Phenothiazines, such as prochlorperazine...
Phenothiazines, such as prochlorperazine...
257
01:22PI3K/mTOR/AKT Signaling Pathway
3.5K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.5K
02:23Abnormal 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