在肺腺癌中,BUB1b通过对肺腺癌酶的耐药性而降低化疗敏感性
Yanguang Ding1,2,3, Jian Gao4, Jun Chen1,2
1Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.
Cell death & disease
|July 23, 2024
概括
BUB1b瘤基因通过稳定NRF2信号传递,促进对铁和化疗的耐药性来驱动肺腺癌 (LUAD) 的进展. 用ML385和化疗准BUB1b可以协同抑制瘤生长.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- BUB1b (BUB1线性检查点血清/三氨酸激酶B) 是多种癌症中确定的瘤基因.
- 对于BUB1b在肺腺癌 (LUAD) 进展中的特定作用及其潜在机制尚未完全理解.
研究的目的:
- 阐明BUB1b促进LUAD进展的机制.
- 调查针对BUB1b作为LUAD治疗策略的潜力.
主要方法:
- 在LUAD组织中分析BUB1b转录和蛋白质水平.
- 在体外和体外的功能增益和丧失测试.
- 研究BUB1b,OTUD3和NRF2.2之间的相互作用.
- 在小鼠模型中评估了一种涉及ML385和化疗的联合治疗策略.
主要成果:
- 在LUAD组织中,BUB1b的表达显著上调,与患者预后不佳相关.
- 通过稳定NRF2通路,BUB1b增强了LUAD细胞的活力,并促进了对铁和化疗的耐药性.
- 联合ML385治疗和化疗显示出协同作用的瘤生长抑制和改善了体内生存率.
结论:
- 通过稳定OTUD3-NRF2复合体,BUB1b作为LUAD中的瘤基因起作用,使其对铁和化疗产生抵抗力.
- 针对BUB1b与化疗结合,为提高LUAD治疗疗效提供了一个有希望的治疗策略.
相关概念视频
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
Targeted 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
Adaptive Mechanisms in Cancer Cells
5.7K
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,...
5.7K
Drugs 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
Cancer Therapies
7.6K
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...
7.6K
Electron Transport Chain: Complex I and II
12.7K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
12.7K


