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肽-配体偶联物在靶向肿瘤细胞中的最新进展和应用。

Recent advances and applications of peptide-agent conjugates for targeting tumor cells.

机构信息

Department of Molecular Medicine, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, 7133654361, Iran.

Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

J Cancer Res Clin Oncol. 2023 Nov;149(16):15249-15273. doi: 10.1007/s00432-023-05144-9. Epub 2023 Aug 15.

Abstract

BACKGROUND

Cancer, being a complex disease, presents a major challenge for the scientific and medical communities. Peptide therapeutics have played a significant role in different medical practices, including cancer treatment.

METHOD

This review provides an overview of the current situation and potential development prospects of anticancer peptides (ACPs), with a particular focus on peptide vaccines and peptide-drug conjugates for cancer treatment.

RESULTS

ACPs can be used directly as cytotoxic agents (molecularly targeted peptides) or can act as carriers (guiding missile) of chemotherapeutic agents and radionuclides by specifically targeting cancer cells. More than 60 natural and synthetic cationic peptides are approved in the USA and other major markets for the treatment of cancer and other diseases. Compared to traditional cancer treatments, peptides exhibit anticancer activity with high specificity and the ability to rapidly kill target cancer cells. ACP's target and kill cancer cells via different mechanisms, including membrane disruption, pore formation, induction of apoptosis, necrosis, autophagy, and regulation of the immune system. Modified peptides have been developed as carriers for drugs, vaccines, and peptide-drug conjugates, which have been evaluated in various phases of clinical trials for the treatment of different types of solid and leukemia cancer.

CONCLUSIONS

This review highlights the potential of ACPs as a promising therapeutic option for cancer treatment, particularly through the use of peptide vaccines and peptide-drug conjugates. Despite the limitations of peptides, such as poor metabolic stability and low bioavailability, modified peptides show promise in addressing these challenges. Various mechanism of action of anticancer peptides. Modes of action against cancer cells including: inducing apoptosis by cytochrome c release, direct cell membrane lysis (necrosis), inhibiting angiogenesis, inducing autophagy-mediated cell death and immune cell regulation.

摘要

背景

癌症作为一种复杂的疾病,对科学界和医学界构成了重大挑战。在包括癌症治疗在内的各种医学实践中,肽类疗法都发挥了重要作用。

方法

本综述概述了抗癌肽(ACPs)的现状和潜在发展前景,特别关注用于癌症治疗的肽疫苗和肽药物偶联物。

结果

ACPs 可以直接用作细胞毒性剂(靶向分子肽),也可以通过特异性靶向癌细胞作为化疗药物和放射性核素的载体(制导导弹)。在美国和其他主要市场,有超过 60 种天然和合成的阳离子肽被批准用于治疗癌症和其他疾病。与传统癌症治疗方法相比,肽类具有高特异性和快速杀伤靶癌细胞的抗癌活性。ACPs 通过不同的机制靶向和杀死癌细胞,包括膜破坏、孔形成、诱导细胞凋亡、坏死、自噬和调节免疫系统。已开发出修饰肽作为药物、疫苗和肽药物偶联物的载体,并在各种临床试验阶段进行了评估,用于治疗不同类型的实体瘤和白血病癌症。

结论

本综述强调了 ACP 作为癌症治疗有前途的治疗选择的潜力,特别是通过使用肽疫苗和肽药物偶联物。尽管肽类存在代谢稳定性差和生物利用度低等局限性,但修饰肽在解决这些挑战方面显示出前景。抗癌肽的各种作用机制。针对癌细胞的作用模式包括:通过细胞色素 c 释放诱导细胞凋亡、直接细胞膜溶解(坏死)、抑制血管生成、诱导自噬介导的细胞死亡和免疫细胞调节。

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