在非小细胞肺癌中,PAI-1调解了对MET向治疗的获得性耐药性
Yin Min Thu1, Ken Suzawa1, Shuta Tomida2
1Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
在MET放大肺癌中获得的对crizotinib的耐药性涉及多种机制,包括SERPINE1过度表达和上皮转移到介质酶. 针对这些途径为非小细胞肺癌提供了潜在的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 在非小细胞肺癌 (NSCLC) 中对MET氨酸激酶抑制剂 (TKIs) 的耐药性机制尚未完全理解.
- MET放大是NSCLC的一个子集中的驱动突变,使MET TKI成为治疗的目标.
研究的目的:
- 研究MET增强NSCLC细胞系中对MET TKIcrizotinib获得的耐药性机制.
- 确定潜在的治疗策略,以克服克里佐替尼抗药性.
主要方法:
- 已确立的克里佐替尼抗性细胞系 (EBC-1和H1993) 来自MET增强NSCLC.
- 利用基因组和转录组分析来识别耐药性因素.
- 验证了假设的耐药性变化和测试的组合疗法.
主要成果:
- 在EBC-1衍生细胞中,SERPINE1 (PAI-1) 过度表达是关键的抵抗机制,对PAI-1抑制和淘汰作出反应.
- 另一种EBC-1亚系通过表皮细胞向介质细胞的过渡与高调节的抗瘤蛋白质表现出耐药性.
- H1993衍生细胞表现出与下游基因激活蛋白激酶通路激活相关的耐药性,这表明MEK抑制剂是治疗选择.
结论:
- 在MET增强NSCLC中对crizotinib获得的耐药性是多因素的.
- 抑制SERPINE1和抑制MEK代表了在特定耐药NSCLC环境中克服crizotinib耐药性的有希望的策略.
更多相关视频
09:38Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
Published on: June 26, 2019
06:51Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
Published on: July 21, 2018
相关概念视频
Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
Targeted Cancer Therapies
There are several types of targeted therapies against...
Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...
Combination Therapies and Personalized Medicine
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...
