相关实验视频

Updated: Jul 25, 2025

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure

Published on: August 11, 2017

在FGFR驱动的泌尿器癌中对选择性FGFR抑制剂的耐药性

Francesco Facchinetti¹, Antoine Hollebecque^2,3, Floriane Braye¹

¹Université Paris-Saclay, Gustave Roussy, Inserm U981, Villejuif, France.

Cancer discovery

|June 28, 2023

概括

尿路癌中对纤维细胞生长因子受体 (FGFR) 抑制剂的耐药性机制涉及FGFR突变和PI3K-mTOR通路改变. 组合疗法显示出克服治疗耐药性的前景.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
遗传学是一个遗传学.

背景情况:

纤维细胞生长因子受体 (FGFR) 抑制剂对于治疗由FGFR驱动的泌尿器癌症至关重要.
对这些抑制剂的耐药性和随后患者复发的机制需要进一步研究.

研究的目的:

在泌尿器癌中识别对选择性FGFR抑制剂耐药性的分子机制.
评估潜在的组合治疗策略,以克服耐药性.

主要方法:

对21名接受FGFR抑制剂治疗的患者的后进展组织和循环瘤DNA (ctDNA) 的分析.
使用Ba/F3细胞模型对已识别的突变进行功能性表征.
在患者衍生模型中对药物组合进行临床前测试.

主要成果:

高频率的FGFR激酶域突变 (33%单个,5%多个) 被确定为一种抵抗机制.
在52%的患者中观察到PI3K-mTOR通路 (TSC1/2,PIK3CA,NF2,PTEN) 的变化.
与PIK3CA E545K观察到的erdafitinib和pictilisib之间的协同作用;erdafitinib-gefitinib组合克服了EGFR介导的抗性.

结论:

FGFR突变和PI3K-mTOR通路改变是尿路癌中对FGFR抑制剂耐药性的关键机制.
临床前数据支持组合策略,如FGFR和PI3K-mTOR抑制,以克服耐药性.
针对绕道阻力通路可能会改善尿路癌患者的治疗结果.

更多相关视频

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib

Published on: June 26, 2019

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors

Published on: December 7, 2014

相关概念视频

Treatment Resistant Cancers

Treatment Resistant Cancers

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...

Targeted Cancer Therapies

Targeted Cancer Therapies

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...

Mitogens and the Cell Cycle

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...