低甲基化剂decitabine使扩散性大B细胞淋巴瘤对venetoclax产生敏感性
Fen Zhu1, Jennifer L Crombie1, Wei Ni1
1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Haematologica
|August 3, 2023
概括
新的研究探讨了将decitabine与venetoclax结合用于治疗扩散性大B细胞淋巴瘤 (DLBCL). 这种组合疗法在克服耐药性和改善DLBCL患者治疗结果方面表现有前途.
科学领域:
- 在瘤学瘤学.
- 血液学 血液学 血液学
- 分子生物学分子生物学
背景情况:
- 扩散性大B细胞淋巴瘤 (DLBCL) 仍然具有挑战性治疗,许多患者无法治愈.
- 抗亡性B细胞淋巴瘤2 (BCL2) 基因在DLBCL中经常失调,但在许多情况下,venetoclax的直接向显示出有限的有效性.
研究的目的:
- 确定venetoclax的合理组合伙伴,以增强其对DLBCL细胞的活性.
- 为了研究dcitabine在DLBCL中增强venetoclax敏感性的机制.
主要方法:
- 动态BH3概况,以评估线粒体的亡原始化.
- 用RNA测序来分析路径的改变.
- 在体外和体内 (异种移植小鼠模型) 增殖试验.
主要成果:
- 德西塔增加了DLBCL细胞中的BCL-2依赖性和线粒体亡原始化.
- 德西塔抑制了PI3K-AKT通路,改变了线粒体膜组成,并诱导了DNA损伤反应.
- 德西他和维尼托克拉克斯的组合在体外和体内证明了对DLBCL细胞增殖的协同抑制.
结论:
- 德西塔因增加阿波托斯原始和BCL-2依赖性而提高DLBCL中的venetoclax敏感性.
- 德西他和维尼托克拉克斯的组合代表了DLBCL的一个有前途的治疗策略.
- 在DLBCL中,需要对decitabine加上venetoclax进行进一步的临床探索.
相关概念视频
Drugs 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
Targeted Cancer Therapies
7.7K
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...
7.7K
Treatment Resistant Cancers
3.3K
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...
3.3K
Combination Therapies and Personalized Medicine
4.9K
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...
4.9K


