相关实验视频

Updated: Sep 11, 2025

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen

Published on: May 30, 2012

TRIM24作为内分泌治疗耐药乳腺癌的治疗标

Nuno Padrão¹, Sebastian Gregoricchio¹, Nils Eickhoff¹

¹Division of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute, Amsterdam 1066 CX, The Netherlands.

Proceedings of the National Academy of Sciences of the United States of America

|August 15, 2025

概括

TRIM24是雌激素受体α (ERα) 活性中的一个关键蛋白. 用降解剂向TRIM24有效治疗ERα阳性乳腺癌,包括内分泌耐药和ESR1突变的形式.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
遗传学遗传学是一个

背景情况:

内分泌疗法耐药性是雌激素受体α (ERα) 阳性乳腺癌的一个主要挑战.
在许多耐治疗瘤中,ERα仍然是主要的驱动因素,需要新的治疗策略.
准ERα转录活性对于克服耐药性至关重要.

研究的目的:

研究TRIM24作为内分泌耐药乳腺癌的潜在治疗标.
阐明TRIM24在ERα转录复合体中的作用及其对瘤生长的影响.
在乳腺癌的临床前模型中评估TRIM24降解剂的疗效.

主要方法:

研究了TRIM24与ERα和辅因子的相互作用.
评估了TRIM24基因干扰对ERα驱动的转录和细胞增殖的影响.
在内分泌反应,耐药性和ESR1突变细胞系模型中使用TRIM24降解剂.
在人类瘤衍生器官模型中验证了TRIM24降解剂的有效性.

主要成果:

TRIM24促进了ERα染色体相互作用,并保持了活性基因素标记 (H3K23ac,H3K27ac).
对TRIM24的遗传破坏抑制了ERα转录程序,并减少了瘤细胞的增殖.
在各种耐药模型中,TRIM24降解剂治疗阻断了ERα输出和生长,包括具有ESR1突变的模型.
TRIM24降解剂在对内分泌反应和耐药的人类瘤有机体中表现出有效性.

结论:

TRIM24对ERα转录复合体的完整性和活性至关重要.
降解TRIM24代表了对原发性和内分泌抵抗性乳腺癌的有前途的治疗策略.
向TRIM24提供了一种新的方法来克服ERα阳性乳腺癌的内分泌治疗阻力.

关键词:

在 TRIM24 中,乳腺癌乳腺癌乳腺癌雌激素受体阿尔法受体是什么异性生物功能蛋白质降解剂治疗耐药性乳腺癌乳腺癌

更多相关视频

Quantifying Antibody-Dependent Cellular Cytotoxicity in a Tumor Spheroid Model: Application for Drug Discovery

Quantifying Antibody-Dependent Cellular Cytotoxicity in a Tumor Spheroid Model: Application for Drug Discovery

Published on: April 26, 2024

Using Mouse Mammary Tumor Cells to Teach Core Biology Concepts: A Simple Lab Module

Using Mouse Mammary Tumor Cells to Teach Core Biology Concepts: A Simple Lab Module

Published on: June 18, 2015

相关概念视频

Targeted Cancer Therapies

Targeted Cancer Therapies

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...

Treatment Resistant Cancers

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...

Combination Therapies and Personalized Medicine

Combination Therapies and Personalized Medicine

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...