EZH2抑制使前列腺癌血统变异演变多样化,并且在抑制疾病进展方面缺乏有效性
Justine J Jacobi1, Kristine M Wadosky2, Neha Jaiswal3
1Roswell Park Cancer Institute, Buffalo, NY, United States.
Cancer research
|November 12, 2025
概括
在晚期前列腺癌 (PrCa) 中,抑制EZH2会增加癌细胞多样性和血统可塑性,这可能会限制EZH2抑制剂治疗这种疾病的有效性.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 晚期前列腺癌 (PrCa) 是男性癌症死亡的主要原因.
- 在PrCa的治疗耐药性往往是由血统可塑性驱动的,癌细胞适应逃避雄激素受体信号传递.
- 基隆甲基转移酶EZH2抑制剂正在临床评估中,用于高级PrCa.
研究的目的:
- 调查EZH2在前列腺癌 (PrCa) 血统可塑性中的作用.
- 确定EZH2抑制对PrCa进展和治疗耐药性的影响.
主要方法:
- 利用PrCa. 的基因工程小鼠模型.
- 分析了人类临床样本.
- 评估了遗传和药理 EZH2 抑制对染色质和基因表达的影响.
- 评估了PrCa血统变异多样性和疾病进展的变化.
主要成果:
- 遗传或药理性抑制EZH2改变的染色质结构.
- EZH2抑制导致扩大了活性转录因子程序.
- 基因表达多样性的增加导致了更多的PrCa谱系变异.
- 在这个模型中,EZH2抑制没有抑制疾病进展或治疗耐药性.
结论:
- EZH2在调节PrCa谱系可塑性方面发挥作用.
- 抑制EZH2增加了PrCa谱系变异的多样性.
- EZH2 抑制剂在治疗易发生血统可塑性的高级 PrCa 时可能具有有限的疗效.
相关概念视频
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
Cancer-Critical Genes II: Tumor Suppressor Genes
9.3K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.3K
Loss of Tumor Suppressor Gene Functions
5.8K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
5.8K
Abnormal Proliferation
5.1K
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...
5.1K
Cancer Therapies
9.8K
Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
9.8K
Tumor Progression
7.2K
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
7.2K


