在儿童癌症中准过度活跃的Ras信号
Anya Levinson1,2, Kevin Shannon1,2, Benjamin J Huang3,4
1Department of Pediatrics, University of California San Francisco, San Francisco, California 94158, USA.
Cold Spring Harbor perspectives in medicine
|July 15, 2024
概括
拉斯突变驱动许多儿科癌症. 抑制Ras通路的向疗法是有希望的,但耐药性需要结合方法和更好的临床前模型来治疗儿童癌症.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 身体RAS突变 (KRAS,NRAS,HRAS) 是儿童和成人癌症的常见驱动因素,具有明显的组织特异性.
- 患有RAS病症的儿童的生殖系NF1和RAS突变为Ras生物学和癌症风险增加提供了洞察力.
研究的目的:
- 审查针对 NF1 或 RAS 突变的儿科癌症的向治疗策略.
- 讨论药物耐药性的挑战和临床前模型的开发.
主要方法:
- 对癌症RAS突变的当前文献的综述.
- 针对性治疗策略和耐药性机制的分析.
- 对儿科瘤学临床前模型开发的讨论.
主要成果:
- 向治疗包括抑制Ras效应器通路,Ras信号输出和Ras后翻译修改/贩运.
- 获得药物耐药性是一个重大挑战,但组合疗法显示出希望.
- 对儿童癌症进行预测的临床前模型的开发是优先考虑的.
结论:
- 针对性疗法为患有RAS通路改变的儿科癌症提供了有希望的途径.
- 克服耐药性需要合理的药物组合和先进的临床前模型.
- 对Ras生物学和治疗向的进一步研究对于改善儿科瘤学的结果至关重要.
相关概念视频
The Ras Gene
6.2K
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...
6.2K
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
Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
mTOR Signaling and Cancer Progression
3.8K
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...
3.8K
Small GTPases - Ras and Rho
3.9K
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
3.9K
MAPK Signaling Cascades
5.4K
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...
5.4K


