巨细胞和血管化决定了肺状细胞癌中对mTOR抑制剂的反应
Morgan R Brady1, Nedas Matulionis1, Heather R Christofk1
1University of California, Los Angeles, Los Angeles, CA, United States.
Cancer research
|December 9, 2025
概括
肺癌细胞通过通过巨型皮诺细胞分裂增加营养吸收来抵抗mTOR抑制剂. 结合mTOR和巨细胞酶抑制剂,以及抗血管生成策略,显示出治疗肺状细胞癌的前景.
科学领域:
- 在瘤学瘤学.
- 癌症新陈代谢 癌症新陈代谢
- 分子生物学分子生物学
背景情况:
- 癌细胞适应新陈代谢以逃避治疗,这给肺癌治疗带来了挑战.
- 对mTOR抑制剂的耐药性是肺状细胞癌 (LUSC) 的关键问题.
研究的目的:
- 在LUSC模型中研究对mTOR抑制剂TAK228的抵抗机制.
- 确定克服LUSC治疗耐药性的策略.
主要方法:
- 使用LUSC细胞系,异种移植和患者衍生异种移植 (PDXs).
- 检查了细胞适应mTOR抑制的情况,重点关注巨细胞和营养吸收.
- 评估的组合疗法包括mTOR,巨细胞和血管生成抑制剂.
主要成果:
- 适应mTOR抑制的LUSC细胞通过上调调节营养获取的巨细胞酶.
- 同时抑制mTOR和巨细胞酶会减少瘤的生长.
- 血管新生通过提供营养物质来抵消联合的mTOR和巨细胞酶抑制.
- 结合抑制mTOR,巨细胞酶和血管生成,在模型中减少了瘤生长.
- 长期使用TAK228和CB-839治疗导致血管化增加和瘤生长反弹.
结论:
- 在LUSC中对mTOR抑制剂的自适应性耐药性涉及通过巨型皮诺细胞形成的代谢重新连接.
- 针对mTOR和巨细胞形成,以及血管生成,为LUSC.提供了潜在的治疗策略.
- 了解这些抵抗机制对于开发有效的个性化癌症疗法至关重要.
更多相关视频
06:51Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
Published on: July 21, 2018
18.5K
09:23Coculture Assays to Study Macrophage and Microglia Stimulation of Glioblastoma Invasion
Published on: October 20, 2016
14.7K
相关概念视频
mTOR Signaling and Cancer Progression
4.6K
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...
4.6K
PI3K/mTOR/AKT Signaling Pathway
5.3K
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...
5.3K
Regulation of Angiogenesis and Blood Supply
3.3K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
3.3K
