相关实验视频

Updated: Sep 19, 2025

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

HS-10375是一种选择性的EGFR C797S氨酸激酶抑制剂,用于高级非小细胞肺癌

Jianhua Zhan¹, Jinhui Xue¹, Lin Wu²

¹State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.

Journal of translational medicine

|June 4, 2025

概括

一种新药,HS-10375,对EGFR C797S突变表现出强烈的活性,这是对肺癌治疗耐药性的常见原因. 早期的人体试验表明,在患有非小细胞肺癌的患者中,有望的安全性和瘤缩小的潜力.

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:

EGFR中的C797S突变是非小细胞肺癌 (NSCLC) 中对第三代EGFR氨酸激酶抑制剂 (TKI) 获得耐药性的关键机制.
目前,没有批准的治疗方法专门针对EGFR C797S突变,造成了大量未满足的医疗需求.

研究的目的:

开发和评估一种新的选择性抑制剂,HS-10375,针对EGFR C797S突变.
评估HS-10375.5的临床前疗效和安全性.
为了确定HS-10375的安全性,耐受性,最大耐受剂量 (MTD) 和初步抗瘤活性,在首次在人身上进行1期临床试验.

主要方法:

临床前评估涉及使用Ba/F3和EGFR突变的患者衍生细胞系进行体外试验,以及在异种移植模型中的体内评估.
一个第一阶段临床试验每天口服HS-10375在6个剂量级 (10-240毫克) 的21天周期内.
主要试验目标侧重于安全性,耐受性和MTD;次要目标包括药理动力学 (PK) 参数和抗瘤活性.

主要成果:

HS-10375在C797S三重突变细胞系中表现出强大的EGFR酸化抑制,并且在双重突变细胞系中具有与现有的TKI相比的/优于的活性.
在EGFR双重或三重C797S突变的细胞中观察到显著的亡,在临床前模型中抑制了瘤生长.
在第一阶段试验 (n=28) 中,MTD 确定为150 mg QD,常见的不良事件包括吐和食欲丧失. 一名患者在经过广泛的先前治疗后显示瘤缩.

结论:

在临床前研究中,HS-10375对EGFR C797S表现出强烈和突变选择性的活性.
第一次在人身上进行的第一阶段试验表明了可接受的安全性概况,并证明了EGFR突变的NSCLC患者的客观反应.
由于C797S突变,HS-10375代表了对NSCLC患者耐受EGFRTKI的有希望的治疗候选者.

关键词:

这是C797S突变.根据TKI的说法,TKI是来自EGFR的.在HS-10375中使用.非小细胞肺癌是非小细胞肺癌.有针对性的治疗.

更多相关视频

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

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids

Published on: November 22, 2021

相关概念视频

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...

Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers

Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers

Receptor tyrosine kinase inhibitors (TKIs) and calcium channel blockers (CCBs) are two critical categories of drugs employed in the treatment of pulmonary artery hypertension (PAH). PAH is a disease that causes high blood pressure in the pulmonary arteries, resulting in chest pain, fatigue, and shortness of breath.
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...