禁食可以通过糖皮质激活提高乳腺癌治疗效率
Nuno Padrão1,2, Tesa M Severson1,2, Sebastian Gregoricchio1,2
1Division of Oncogenomics, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Nature
|December 10, 2025
概括
定期禁食通过激活葡萄糖皮质受体 (GR) 信号,延缓药物耐药性和促进瘤回归来增强雌激素受体阳性乳腺癌的内分泌治疗. 这表明皮质类固醇可以帮助治疗.
科学领域:
- 癌症学
- 内分泌学
- 表观遗传学
背景情况:
- 雌激素受体α (ERα) 阳性乳腺癌依赖于ERα激活,内分泌疗法作为主要治疗方法.
- 获得对内分泌疗法的耐药性是一个重要的临床挑战,导致瘤的进展.
- 定期禁食有助于提高内分泌疗法的有效性和延迟耐药性,但机制尚不清楚.
研究的目的:
- 阐明定期禁食增强ERα阳性乳腺癌内分泌治疗的机制.
- 研究表观遗传重编程和特定受体信号通路在禁食中介抗瘤作用中的作用.
- 探索作为辅助疗法的向葡萄皮质受体 (GR) 激活的潜力.
主要方法:
- 使用ERα阳性乳腺癌异种移植模型与内分泌疗法和定期禁食相结合.
- 分析了表观遗传重编程,基因表达和受体信号 (GR,AP-1).
- 进行了GR淘汰试验,并测试了外源的GR连接剂.
- 对模仿禁食饮食的患者样本进行了评估,以检测荷尔蒙变化和瘤标志物的相关性.
主要成果:
- 禁食结合内分泌疗法诱导了表观遗传重编程,激活了葡萄皮质受体 (GR) 和孕激素受体信号,同时降低了AP-1活性.
- 在体内,GR激活对禁食与他莫西芬结合的抗瘤作用至关重要.
- 外源性GR配体模仿禁食增强抗雌激素作用,促进瘤回归.
- 患有类似禁食饮食的患者表现出孕激素和皮质醇的增加,GR激活与瘤增殖相反相关.
结论:
- 葡萄糖皮质体受体 (GR) 的激活在促进禁食对乳腺癌内分泌治疗的有益作用方面发挥着关键作用.
- 禁食通过GR驱动的基因程序增强了抗雌激素作用,延迟了药物耐药性.
- 作为ERα阳性乳腺癌内分泌治疗的辅助剂,需要进行皮质类固醇的研究.
相关概念视频
Hypoglycemia and Glucagon
772
Without prolonged fasting, healthy individuals maintain blood glucose levels above 3.5 mM due to a well-adapted neuroendocrine counterregulatory system that effectively prevents acute hypoglycemia, a potentially life-threatening condition. The primary clinical scenarios for hypoglycemia encompass diabetes treatment, inappropriate production of endogenous insulin or insulin-like substances by tumors, and the use of glucose-lowering agents in non-diabetic individuals. Notably, hypoglycemia in the...
772
Metabolic States of the Body: Fasting and Starvation
2.6K
During the initial hours of fasting, the body uses up its glycogen stores as an energy source. Once these glycogen reserves are depleted, the body begins breaking down stored triglycerides and structural proteins. During this stage, glycerol becomes a key substrate for gluconeogenesis, while free fatty acids undergo beta-oxidation to provide energy for tissues, such as skeletal muscle. In the fasting state, the body spares protein breakdown as much as possible to conserve muscle and structural...
2.6K
Hormones Regulating Blood Glucose
6.3K
Insulin is released by beta cells of the pancreas when blood glucose levels are high. It facilitates glucose absorption and utilization in insulin-dependent cells with insulin receptors on their plasma membranes. Insulin promotes glucose uptake by increasing the number of glucose transport proteins in the cell membrane, allowing glucose to enter the cell. As a result, glucose utilization and ATP production are enhanced.
In addition to accelerating glucose uptake and utilization, insulin has...
In addition to accelerating glucose uptake and utilization, insulin has...
6.3K
Adaptive Mechanisms in Cancer Cells
6.9K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
6.9K
Drugs for Treatment of Crohn's Disease in IBD Using Glucocorticoids
408
Glucocorticoids, a class of anti-inflammatory drugs, are pivotal in treating moderate to severe Crohn's disease by inducing remission. They exhibit their anti-inflammatory action by inhibiting the production of inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, and chemokines like IL-8. In addition, they reduce the expression of inflammatory cell adhesion molecules and inhibit gene transcription of nitric oxide synthase, phospholipase A2, cyclooxygenase-2...
408
Targeted Cancer Therapies
8.6K
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...
8.6K


