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靶向基质金属蛋白酶作为癌症治疗方法的策略。

Strategies to Target Matrix Metalloproteinases as Therapeutic Approach in Cancer.

作者信息

Piperigkou Zoi, Manou Dimitra, Karamanou Konstantina, Theocharis Achilleas D

机构信息

Biochemistry, Biochemical Analysis & Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patras, Greece.

出版信息

Methods Mol Biol. 2018;1731:325-348. doi: 10.1007/978-1-4939-7595-2_27.

Abstract

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that are capable of degrading numerous extracellular matrix (ECM) components thus participating in physiological and pathological processes. Apart from the remodeling of ECM, they affect cell-cell and cell-matrix interactions and are implicated in the development and progression of various diseases such as cancer. Numerous studies have demonstrated that MMPs evoke epithelial to mesenchymal transition (EMT) of cancer cells and affect their signaling, adhesion, migration and invasion to promote cancer cell aggressiveness. Various studies have suggested MMPs as suitable targets for treatment of malignancies, and several MMP inhibitors (MMPIs) have been developed. Although initial trials have failed to establish MMPIs as anticancer agents due to lack of specificity and side effects, new MMPIs have been developed with improved action that are currently being investigated. Furthermore, novel strategies that target MMPs for improving drug delivery and regulating their activity in tumors are presented. This review summarizes the implication of MMPs in cancer progression and discusses the advancements in their targeting.

摘要

基质金属蛋白酶(MMPs)是一类锌依赖性内肽酶,能够降解多种细胞外基质(ECM)成分,从而参与生理和病理过程。除了细胞外基质重塑外,它们还影响细胞间和细胞与基质的相互作用,并与各种疾病(如癌症)的发生和发展有关。大量研究表明,基质金属蛋白酶可引发癌细胞的上皮-间质转化(EMT),并影响其信号传导、黏附、迁移和侵袭,从而促进癌细胞的侵袭性。各种研究表明,基质金属蛋白酶是治疗恶性肿瘤的合适靶点,并且已经开发了几种基质金属蛋白酶抑制剂(MMPIs)。尽管最初的试验由于缺乏特异性和副作用而未能将基质金属蛋白酶抑制剂确立为抗癌药物,但目前已经开发出了作用有所改善的新型基质金属蛋白酶抑制剂,正在进行研究。此外,还提出了针对基质金属蛋白酶的新策略,以改善药物递送并调节其在肿瘤中的活性。本综述总结了基质金属蛋白酶在癌症进展中的作用,并讨论了针对它们的研究进展。

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