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近年来,在细胞外基质降解和合成抑制策略方面的进展,为改善实体瘤的治疗提供了可能。

Recent Advances in Strategies for Extracellular Matrix Degradation and Synthesis Inhibition for Improved Therapy of Solid Tumors.

机构信息

PK-PD Toxicology & Formulation Division, CSIR- Indian Institute of Integrative Medicine, Canal Road, Jammu, J&K, 180001, India.

出版信息

Curr Pharm Des. 2020;26(42):5456-5467. doi: 10.2174/1381612826666200728141601.

Abstract

Despite a great deal of efforts made by researchers and the advances in the technology, the treatment of cancer is very challenging. Significant advances in the field of cancer therapeutics have been made but due to the complexity of solid tumor microenvironment, specially their dense extracellular matrix (which makes the conditions favorable for cancer growth, metastasis and acts as a barrier to the chemotherapeutic drugs as well as nanomedicine), the treatment of solid tumors is difficult. Overexpression of extracellular matrix components such as collagen, hyaluronan and proteoglycans in solid tumor leads to high interstitial fluid pressure, hypoxia, vascular collapse and poor perfusion which hinder the diffusion and convection of the drugs into the tumor tissue. This leads to the emergence of drug resistance and poor antitumor efficacy of chemotherapeutics. A number of approaches are being investigated in order to modulate this barrier for improved outcome of cancer chemotherapy. In this review, recent advances in the various approaches for the modulation of the extracellular matrix barrier of the solid tumor are covered and significant findings are discussed in an attempt to facilitate more investigations in this potential area to normalize the tumor extracellular matrix for improving drug exposure to solid tumor.

摘要

尽管研究人员付出了巨大努力并推动了技术进步,癌症的治疗仍然极具挑战性。癌症治疗领域取得了重大进展,但由于实体瘤微环境的复杂性,特别是其密集的细胞外基质(这为癌症生长、转移创造了有利条件,并成为化疗药物和纳米医学的障碍),实体瘤的治疗仍然很困难。在实体瘤中,细胞外基质成分如胶原蛋白、透明质酸和蛋白聚糖的过度表达会导致间质液压力升高、缺氧、血管塌陷和灌注不良,从而阻碍药物扩散和对流进入肿瘤组织。这导致了耐药性的出现和化疗药物抗肿瘤效果不佳。目前正在研究多种方法来调节这种屏障,以提高癌症化疗的效果。本文综述了近年来在调节实体瘤细胞外基质屏障方面的各种方法的最新进展,并讨论了一些重要的发现,以期促进该领域的进一步研究,使肿瘤细胞外基质正常化,从而提高药物对实体瘤的暴露度。

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