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开发治疗性蛋白以精准杀伤癌细胞。

Evolving therapeutic proteins to precisely kill cancer cells.

机构信息

Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, 47500 Subang Jaya, Selangor, Malaysia.

School of Life Sciences, University of Essex, Wivenhoe Park, Colchester CO4 3SQ, UK.

出版信息

J Control Release. 2022 Nov;351:779-804. doi: 10.1016/j.jconrel.2022.09.066. Epub 2022 Oct 10.

Abstract

The established cancer treatment strategy in clinical setting is based on chemo and radiation therapy, having limitations due to severe side-effects and drug-resistance. Small molecule chemo-drugs target any fast-dividing cells irrespective of healthy or defective origin. As a result, a substantial amount of healthy tissue is also destroyed. Moreover, failure to recognize the heterogeneity of tumour tissue results in drug-resistance over the course of time. On the other hand, peptides and proteins actively target somatic changes that are signature to any specific tumour tissue. Development and metastasis of cancer cells require unique disruption/alteration of protein activity. Identification of those wild and cancerous genotypes and phenotypes is the key to establishing easy 'targets' for protein based targeted therapeutics. The approach is cytostatic and tissue specific, which reduces drug toxicity. Biopharmaceutical products based on proteins and peptides are slowly re-directing oncology from cytotoxic small molecular treatment approach to target oriented cytostatic strategy. This review focuses on current and upcoming peptide and protein-based precision therapeutics. At the same time, the study also shades light on the technological advancement in the field of protein and peptide-based therapeutics.

摘要

临床上既定的癌症治疗策略基于化疗和放疗,但由于严重的副作用和耐药性,存在一定局限性。小分子化疗药物针对任何快速分裂的细胞,无论其起源是健康的还是有缺陷的。因此,大量的健康组织也会被破坏。此外,由于未能识别肿瘤组织的异质性,随着时间的推移会产生耐药性。另一方面,肽和蛋白质主动针对肿瘤组织特有的体细胞变化进行靶向治疗。癌细胞的发展和转移需要独特地破坏/改变蛋白质的活性。鉴定这些野生型和癌变的基因型和表型是建立基于蛋白质的靶向治疗的简便“靶点”的关键。这种方法具有细胞抑制作用和组织特异性,可降低药物毒性。基于蛋白质和肽的生物制药产品正逐渐将肿瘤学从细胞毒性小分子治疗方法重新引导到针对目标的细胞抑制策略。本综述重点介绍了当前和即将出现的基于肽和蛋白质的精准治疗方法。同时,该研究还揭示了基于蛋白质和肽的治疗领域的技术进步。

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