阿贝马西克利布在帕尔博西克利布抗性激素受体阳性转移性乳腺癌中有效
Juliana Navarro-Yepes1, Nicole M Kettner1, Xiayu Rao2
1Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Cancer research
|June 29, 2023
概括
使用循环素依赖性激酶4/6抑制剂 (CDK4/6i) 进行序列疗法,对转移性乳腺癌显示出有前途. 抗Palbociclib的细胞可能会对abemaciclib做出反应,在进展后提供新的治疗选择.
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:
- 循环素依赖性激酶4/6抑制剂 (CDK4/6i) 加上内分泌疗法 (ET) 是HR+,HER2-转移性乳腺癌 (MBC) 的标准.
- 对CDK4/6i加ET的耐药性是一个重大的临床挑战,在进展后限制了治疗选择.
- 对不同CDK4/6的独特抗药机制可能允许进行连续的治疗策略.
研究的目的:
- 调查HR+,HER2-MBC.中对palbociclib和abemaciclib的独特耐药性途径.
- 确定 CDK4/6 抑制剂进展的患者的潜在治疗策略.
- 为了评估顺序CDK4/6i治疗的疗效.
主要方法:
- 在实验室中产生抗皮基 (PR) 和抗皮基 (AR) 的细胞系.
- 在体内患者衍生异种移植 (PDX) 和体外PDX衍生器官 (PDxO) 的发展,这些患者在CDK4/6i上进展.
- 耐药模型的转录和蛋白质分析.
- 来自52名患者队列的临床数据分析,这些患者接受了连续的CDK4/6i治疗.
主要成果:
- PR和AR细胞表现出明显的转录组和蛋白组特征,表明对抑制剂的敏感性差异.
- PR细胞上调了G2-M通路并对abemaciclib作出反应,而AR细胞上调了氧化酸化 (OXPHOS) 并对OXPHOS抑制剂作出反应.
- 来自palbociclib进展的患者的PDX和器官模型仍然对abemaciclib敏感.
- 在palbociclib之后的顺序abemaciclib疗法在患者队列中显示出临床益处.
结论:
- 帕尔博西克利布耐药性与特定途径的激活有关,不一定是个别的遗传改变.
- 连续的CDK4/6i治疗,特别是abemaciclib后palbociclib,是MBC患者在初始CDK4/6i治疗中进展的可行策略.
- 这些发现支持对 HR+,HER2- MBC.的顺序CDK4/6i疗法进行进一步的临床研究.
更多相关视频
09:19Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
8.7K
08:59Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
Published on: December 11, 2017
7.3K
相关概念视频
02:57Targeted Cancer Therapies
7.7K
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...
7.7K
02:34Inhibition of Cdk Activity
4.8K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.8K
02:56Treatment 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