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肿瘤血管生成与 VEGFR-2:机制、途径及当前生物治疗干预措施。

Tumor Angiogenesis and VEGFR-2: Mechanism, Pathways and Current Biological Therapeutic Interventions.

机构信息

Department of Biosciences, Integral University, Lucknow-226026, UP, India.

Novel Global Community Educational Foundation, Peterlee Place, Hebersham, NSW 2770, Australia.

出版信息

Curr Drug Metab. 2021;22(1):50-59. doi: 10.2174/1389200221666201019143252.

Abstract

BACKGROUND

Angiogenesis, involving the formation of new blood vessels from preexisting vessels, caters an important biological phenomenon for the growth and development of bodily structures in the human body. Regulation of angiogenesis in non-pathological conditions takes place through a well-defined balanced angiogenic-switch, which upon exposure to various pathological conditions may get altered. This makes the cells change their normal behavior resulting in uncontrolled division and angiogenesis.

METHODS

The current review tries to present a brief framework of angiogenesis and tumor progression phenomenon along with the latest therapeutic interventions against VEGFR-2 and its future directions.

RESULTS

The tumor angiogenic pathways functioning in diverse mechanisms via sprouting angiogenesis, intussusceptive angiogenesis, vascular co-option, vascular mimicry, and glomeruloid angiogenesis are normally activated by varied angiogenic stimulators and their receptors are interrelated to give rise to specialized signaling pathways. Amongst these receptors, VEGFR-2 is found as one of the key, critical mediators in tumor angiogenesis and is seen as a major therapeutic target for combating angiogenesis. Though a number of anti-angiogenic drugs like Ramucirumab, Sunitinib, Axitinib, Sorafenib, etc. showing good survival rates have been developed and approved by FDA against VEGFR-2, but these have also been found to be associated with serious health effects and adverse reactions.

CONCLUSION

An improved or alternative treatment is needed shortly that has a higher survival rate with the least side effects. Innovative strategies, including personalized medicine, nano-medicine, and cancer immunotherapy have also been outlined as an alternative treatment with a discussion on advancements and improvements required for their implementation methods.

摘要

背景

血管生成是指从预先存在的血管中形成新的血管,它是人体结构生长和发育的重要生物学现象。在非病理条件下,血管生成受到严格控制的平衡血管生成开关的调节,而在各种病理条件下,这种调节可能会发生改变。这使得细胞改变正常行为,导致不受控制的分裂和血管生成。

方法

本综述试图简要介绍血管生成和肿瘤进展现象的框架,以及针对 VEGFR-2 的最新治疗干预措施及其未来方向。

结果

在不同机制下发挥作用的肿瘤血管生成途径,如发芽血管生成、内套血管生成、血管选择、血管模拟和肾小球样血管生成,通常被各种血管生成刺激物激活,其受体相互关联,产生专门的信号通路。在这些受体中,VEGFR-2 被认为是肿瘤血管生成的关键和关键介质之一,被视为对抗血管生成的主要治疗靶点。尽管已经开发并由 FDA 批准了许多针对 VEGFR-2 的抗血管生成药物,如雷莫芦单抗、舒尼替尼、阿昔替尼、索拉非尼等,这些药物具有较好的生存率,但也发现它们与严重的健康影响和不良反应有关。

结论

需要尽快开发出一种改进或替代的治疗方法,这种方法具有更高的生存率和最小的副作用。个性化医学、纳米医学和癌症免疫疗法等创新策略也被概述为替代治疗方法,并讨论了实施方法所需的改进和进步。

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