同时抑制ALK和SRC激酶会破坏ALK肺瘤细胞蛋白质组
Alberto Diaz-Jimenez1, Maria Ramos1, Barbara Helm2
1Division of Molecular Thoracic Oncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany; Ruprecht Karls University of Heidelberg, Heidelberg 69120, Germany.
针对ALK和SRC激酶,可以克服ALK阳性肺癌的抗性. 这种联合治疗,共同向形淋巴瘤激酶 (ALK) 和SRC,改善治疗反应,为患者提供新的希望.
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:
- 精密瘤学已经推进了ALK阳性肺癌治疗.
- 耐药性仍然是一个重大的临床挑战,由突变或替代途径驱动.
- EML4-ALK变体和SRC激酶激活与治疗耐药性有关.
研究的目的:
- 为了研究ALK阳性肺癌的耐药机制.
- 评估共同准ALK和SRC激酶的疗效.
主要方法:
- 已建立的EML4-ALK变异的小鼠瘤衍生细胞模型.
- 进行蛋白质基因分析以确定抗性机制.
- 在体外和体内评估ALK和SRC共同准的效果.
主要成果:
- 在EML4-ALK变异3中,对ALK抑制剂的反应较差.
- 布里加替尼治疗提高了SRC激酶的调节,这表明它在耐药性方面的作用.
- 同时准ALK和SRC在小鼠和患者衍生模型中显著抑制瘤生长.
- 组合疗法通过蛋白质和mTOR途径调节诱导细胞死亡.
结论:
- 同时准ALK和SRC激酶是克服ALK阳性肺癌耐药性的有希望的策略.
- 这种方法有可能改善耐火病例的临床结果.
- 了解蛋白质组景观对于开发有效的组合疗法至关重要.
更多相关视频
09:49Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing
Published on: July 5, 2019
07:42Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
Published on: September 19, 2018
相关概念视频
PI3K/mTOR/AKT Signaling Pathway
Targeted Cancer Therapies
There are several types of targeted therapies against...
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
