一个强大的最佳控制框架,用于控制异常RTK信号通路在食道癌症
Souvik Roy1, Zui Pan2, Naif Abu Qarnayn3
1Department of Mathematics, The University of Texas at Arlington, Arlington, TX, 76019-0407, USA. souvik.roy@uta.edu.
Journal of mathematical biology
|January 5, 2024
概括
这项研究引入了个性化食道癌症治疗的新框架,优化了对表皮生长因子 (EGF) 和血管内皮生长因子 (VEGF) 途径的治疗方法,使用了新的药理动力学模型和药物组合.
科学领域:
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
- 计算生物学 计算生物学
背景情况:
- 食道癌症的治疗面临着挑战,因为表皮生长因子 (EGF) 和血管内皮生长因子 (VEGF) 等异常信号通路.
- 需要个性化治疗策略,以有效地针对这些特定的信号机制,并考虑到患者的异质性.
研究的目的:
- 在食道癌症中开发个性化最佳治疗策略的新框架.
- 创建一个药理动力学模型,将EGF和VEGF信号的患者特异性纳入其中.
- 使用多步计算方法设计和验证最佳疗法.
主要方法:
- 开发了一种药理动力学模型,考虑信号通路异质性.
- 采用了三步过程,包括受约束优化,灵敏度分析和最佳控制.
- 利用离散患者数据进行模型参数估计.
- 将Trastuzumab (抗EGF) 和Bevacizumab (抗VEGF) 纳入治疗模拟模型中.
主要成果:
- 通过敏感性分析,成功确定了EGF和VEGF受体进化的关键敏感参数.
- 证明了框架能够推导出最佳治疗策略的能力.
- 数字结果显示了用于向治疗的Trastuzumab和Bevacizumab组合的效率.
结论:
- 拟议的框架为食道癌的个性化治疗提供了一个有希望的方法.
- 新的药理动力学模型和优化策略有效地针对异常的EGF和VEGF信号通路.
- 基于计算建模,Trastuzumab和Bevacizumab的联合治疗显示出显著的潜力.
相关概念视频
03:03mTOR 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
01:19Interactions Between Signaling Pathways
6.3K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.3K
02:38Mitogens and the Cell Cycle
6.5K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.5K
01:26Receptor Tyrosine Kinases
13.0K
Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
13.0K
01:07MAPK Signaling Cascades
5.5K
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...
5.5K
01:27Transducer Mechanism: Enzyme-Linked Receptors
2.5K
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
2.5K