在Osimertinib治疗的EGFR突变NSCLC中对抗性突变进行PIKing和AKTing
Natalie I Vokes1,2, Xiuning Le1, Timothy A Yap1,3,4,5
1Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
概括
高率的PI3K-AKT路径突变降低了osimertinib在EGFR突变的非小细胞肺癌中的有效性. AKT 抑制剂 capivasertib 显示出克服这种抗性的潜力,支持 AKT 抑制剂的发展.
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:
- 奥西默提尼布是一种针对EGFR突变非小细胞肺癌 (NSCLC) 的向疗法.
- PI3K-AKT路径突变越来越多地被认为是对EGFR抑制剂耐药性的机制.
- 了解耐药机制对于改善NSCLC治疗结果至关重要.
研究的目的:
- 研究PI3K-AKT通路突变对EGFR突变NSCLC中奥西默蒂尼布敏感性的流行率和影响.
- 为了评估AKT抑制剂capivasertib在克服由这些突变驱动的osimertinib耐药性的疗效.
主要方法:
- 从FLAURA和AURA3 osimertinib临床试验中分析突变数据.
- 确定突变的临床前验证及其对奥西默蒂尼布敏感性的影响.
- 在体外和体内研究评估capivasertib在耐药模型中的抗瘤活性.
主要成果:
- 在接受 osimertinib 治疗的患者中发现了PI3K-AKT 途径突变的高率.
- 这些突变在临床前得到验证,在EGFR突变的NSCLC中赋予了对 osimertinib 的耐药性.
- 在临床前的模型中,capivasertib有效地克服了 osimertinib 的耐药性.
结论:
- PI3K-AKT通路的激活是EGFR突变NSCLC中ozimertinib耐药性的重要机制.
- 用像capivasertib这样的抑制剂向AKT通路代表了对抗性NSCLC的有希望的治疗策略.
- 需要对AKT抑制剂与奥西默蒂尼布结合或之后进行进一步的临床研究.
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
7.9K
09:38Establishing 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
8.8K
相关概念视频
Treatment Resistant Cancers
3.3K
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...
3.3K
Mismatch Repair
4.8K
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
4.8K
Cancer-Critical Genes II: Tumor Suppressor Genes
7.4K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
7.4K
Targeted Cancer Therapies
7.5K
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...
There are several types of targeted therapies against...
7.5K
