针对TGF-β异型治疗癌症治疗干预的进展和挑战:基于机制的视角
David Danielpour1,2,3
1Case Comprehensive Cancer Center Research Laboratories, The Division of General Medical Sciences-Oncology, Case Western Reserve University, Cleveland, OH 44106, USA.
Pharmaceuticals (Basel, Switzerland)
|April 27, 2024
概括
转化生长因子-β (TGF-β) 异型具有不同的作用,但目前的疗法通常针对所有三种. 本综述强调了异形特异性功能,并倡导针对性癌症疗法.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 在瘤学瘤学.
背景情况:
- 转化生长因子-β (TGF-β) 家族包括三个不同的哺乳动物异型 (TGF-β1,TGF-β2,TGF-β3),每个都有独特的调节元素和关键的生理功能.
- 尽管它们在发育和细胞过程中起着至关重要的作用,但失调的TGF-β表达与纤维化和癌症进展等疾病有关.
- 目前的治疗策略往往无法区分TGF-β异型,针对所有三种共同而不是特定的放松管制的异型.
研究的目的:
- 提供TGF-β场的历史概述,强调每种异构体的经常被忽视的独特功能.
- 介绍TGF-β研究的现状,重点关注异构体在疾病病理学,特别是癌症中的特定作用.
- 批判性地评估现有的TGF-β向癌症疗法,并倡导精细化,基于机制的方法.
主要方法:
- 文献综述和对TGF-β异型,它们的功能和治疗向现有研究的综合.
- 对TGF-β研究的历史观点和当前趋势的分析.
- 评估当前TGF-β抑制剂在癌症治疗中的有效性和局限性.
主要成果:
- 每个TGF-β异型 (1,2,3) 都具有独特的生物功能,对细胞生长,免疫反应和分化至关重要.
- TGF-β信号的失调是病理状况的重要驱动因素,包括纤维化和瘤转移.
- 现有的TGF-β抑制剂往往缺乏特异性,向所有异构体,并阻碍癌症的治疗潜力,因为需要保留生理作用.
结论:
- 更深入地了解异形特异性TGF-β功能对于开发有效的癌症疗法至关重要.
- 未来的治疗策略必须专注于针对特定的放松管制的异构体和与疾病相关的途径组件.
- 基于机制和精细的方法对于提高TGF-β向癌症治疗的疗效至关重要,同时最大限度地减少非向效应.
相关概念视频
TGF - β Signaling Pathway
7.3K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.3K
Targeted Cancer Therapies
7.6K
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...
7.6K
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF
134
Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab...
134
The Tumor Microenvironment
6.6K
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
6.6K
Tumor Immunotherapy
520
Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
520
Transducer Mechanism: Enzyme-Linked Receptors
2.4K
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:
2.4K


