相关实验视频

Updated: Jul 8, 2025

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Utilizing 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

在KRAS G12C突变驱动的非小细胞肺癌 (NSCLC) 中

Rafael Rosell¹, Jordi Codony-Servat², Jessica González³

¹Germans Trias i Pujol Research Institute, Badalona (IGTP), Spain; IOR, Hospital Quiron-Dexeus, Barcelona, Spain.

Critical reviews in oncology/hematology

|December 10, 2023

概括

克拉斯G12C抑制剂在非小细胞肺癌 (NSCLC) 中显示部分反应. 通过信号通路重新连接而出现适应性抵抗,涉及MRAS:SHOC2:PP1C复合体,提供新的治疗点.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
药物发现药物发现药物发现

背景情况:

KRAS G12C突变驱动非小细胞肺癌 (NSCLC),但易受适应性耐药性的影响.
抵抗机制包括受体氨酸激酶激活 (EGFR,MET) 和信号通路重新连接.
这种MRAS:SHOC2:PP1C复合体与对KRAS G12C抑制剂,如sotorasib的耐药性有关.

研究的目的:

阐明NSCLC中对KRAS G12C抑制剂的适应性耐药性的机制.
在MRAS:SHOC2:PP1C复合体和相关途径中确定新的治疗点.
探索针对这些途径对化疗和免疫治疗疗效的影响.

主要方法:

在分析中使用MRAS:SHOC2:PP1C复合物的高分辨率晶体结构.
研究与MRAS激活相关的Scribble,Hippo和STAT3信号通路.
探索HUWE1和含瓦洛蛋白 (VCP) 在调节MRAS复合体中的作用.

主要成果:

KRAS G12C抑制剂治疗触发了MRAS:SHOC2:PP1C复合体,由Scribble路径的改变和YAP激活驱动.
MRAS激活与STAT3信号交织在一起,并由VCP重新激活.
HUWE1作为MRAS:SHOC2:PP1C复合物的负调节剂.

结论:

准MRAS:SHOC2:PP1C复合体及其调节途径是一个有希望的策略,以克服KRAS G12C突变NSCLC中的适应性抵抗.
了解这些抗药性机制对于开发与现有药物如索托拉西布,卡博普拉丁和帕克利塔克塞尔的有效组合疗法至关重要.
与KRAS G12C同时发生的STK11/LKB1突变可能会减少对免疫检查点抑制剂的反应,突出显示需要个性化治疗方法.

关键词:

AQP5 AQP5 AQP5 AQP5 AQP5 AQP5 AQP5 AQP5 AQP5 AQP5 AQP5 AQP5 AQP5 胡威1 胡威1 是一个免疫治疗是一种免疫疗法.在KRAS G12C中使用.马拉斯 (MRAS) 是一个很好的方法.在NSCLCLC中,我们可以看到NSCLCLC.在RGS3中使用RGS3.这就是SHOC2的原因.在STK11/LKB1中.这是一个VCPVCP.

更多相关视频

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors

Published on: September 20, 2016

Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer

Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer

Published on: September 8, 2023

相关概念视频

The Ras Gene

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...

Adaptive Mechanisms in Cancer Cells

Adaptive Mechanisms in Cancer Cells

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,...

Abnormal Proliferation

Abnormal Proliferation

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...