在非小细胞肺癌中出现新的激酶激活基因事件
Elena V Preobrazhenskaya1,2, Rimma S Mulkidjan1, Fyodor A Zagrebin1
1Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, 197758 St.-Petersburg, Russia.
Exploration of targeted anti-tumor therapy
|July 15, 2025
概括
这项研究在非小细胞肺癌 (NSCLC) 中发现了很少的新激酶激活变异. 研究人员发现了罕见的基因融合,但大多数变化都是独一无二的,这表明NSCLC中有限的新可药物标.
科学领域:
- 在瘤学瘤学.
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
背景情况:
- 非小细胞肺癌 (NSCLC) 仍然是癌症死亡的主要原因.
- 识别新的可用药物点对于改善NSCLC治疗结果至关重要.
- 以前的研究已经确定了几种可操作的突变,但NSCLC患者的一个子集缺乏这些已知的变化.
研究的目的:
- 在一组NSCLC患者中识别新的,潜在的可用药物的激酶激活变异.
- 调查从年轻发病和/或女性非吸烟者中NSCLCs的遗传变化,这些人经常呈现出明显的分子形状.
- 评估NSCLC中特定基因融合和激酶域突变的频率.
主要方法:
- 在89个NSCLC样本中的650个蛋白激酶基因上进行了RNA下一代测序 (NGS).
- 从患者中选择了常见激活突变 (例如EGFR,ALK,ROS1) 负的样本.
- 在更大的NSCLC队列中进一步分析了已识别的转位,并使用CADD得分评估了酶域突变.
主要成果:
- RNA测序发现了32个框架内重排序,包括17个影响氨酸激酶域的转位.
- 在一个较大的队列中发现了两个具有ADK::KAT6B重组的额外瘤和一个具有RPS6KB1::VMP1融合的瘤.
- 在551多种额外的NSCLC中没有发现复发性激酶域突变 (CADD>25),并且没有重新观察到CLIP1::LTK融合.
结论:
- 这项研究强调了NSCLC中以前未被识别的激酶激活突变的稀缺性.
- 确定的基因融合 (ADK::KAT6B,RPS6KB1::VMP1) 是罕见的事件.
- 可能需要进一步的研究来探索其他非酶驱动的NSCLC治疗策略.
相关概念视频
The Ras Gene
6.4K
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...
Ras is a...
6.4K
Cancer-Critical Genes I: Proto-oncogenes
9.2K
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...
9.2K
MAPK Signaling Cascades
6.1K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
6.1K
PI3K/mTOR/AKT Signaling Pathway
4.0K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
4.0K
mTOR Signaling and Cancer Progression
3.9K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.9K
Cancer-Critical Genes II: Tumor Suppressor Genes
8.1K
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...
8.1K


