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用于肺癌的 HuR 靶向治疗的药物递送方法。

Drug delivery approaches for HuR-targeted therapy for lung cancer.

机构信息

Department of Pathology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.

Department of Pathology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Graduate Program in Biomedical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.

出版信息

Adv Drug Deliv Rev. 2022 Jan;180:114068. doi: 10.1016/j.addr.2021.114068. Epub 2021 Nov 22.

Abstract

Lung cancer (LC) is often diagnosed at an advanced stage and conventional treatments for disease management have limitations associated with them. Novel therapeutic targets are thus avidly sought for the effective management of LC. RNA binding proteins (RBPs) have been convincingly established as key players in tumorigenesis, and their dysregulation is linked to multiple cancers, including LC. In this context, we review the role of Human antigen R (HuR), an RBP that is overexpressed in LC, and further associated with various aspects of LC tumor growth and response to therapy. Herein, we describe the role of HuR in LC progression and outline the evidences supporting various pharmacologic and biologic approaches for inhibiting HuR expression and function. These approaches, including use of small molecule inhibitors, siRNAs and shRNAs, have demonstrated favorable results in reducing tumor cell growth, invasion and migration, angiogenesis and metastasis. Hence, HuR has significant potential as a key therapeutic target in LC. Use of siRNA-based approaches, however, have certain limitations that prevent their maximal exploitation as cancer therapies. To address this, in the conclusion of this review, we provide a list of nanomedicine-based HuR targeting approaches currently being employed for siRNA and shRNA delivery, and provide a rationale for the immense potential therapeutic benefits offered by nanocarrier-based HuR targeting and its promise for treating patients with LC.

摘要

肺癌(LC)通常在晚期诊断,并且用于疾病管理的常规治疗方法存在局限性。因此,迫切需要新的治疗靶点来有效治疗 LC。RNA 结合蛋白(RBPs)已被确凿地确立为肿瘤发生的关键参与者,其失调与多种癌症有关,包括 LC。在这种情况下,我们回顾了人抗原 R(HuR)的作用,HuR 是一种在 LC 中过度表达的 RBP,并且与 LC 肿瘤生长和对治疗的反应的各个方面进一步相关。在此,我们描述了 HuR 在 LC 进展中的作用,并概述了支持各种抑制 HuR 表达和功能的药理学和生物学方法的证据。这些方法包括使用小分子抑制剂、siRNA 和 shRNA,已证明在减少肿瘤细胞生长、侵袭和迁移、血管生成和转移方面具有良好的效果。因此,HuR 作为 LC 的关键治疗靶点具有重要潜力。然而,基于 siRNA 的方法的使用存在某些限制,这些限制阻止了它们作为癌症疗法的最大利用。为了解决这个问题,在本综述的结论部分,我们提供了当前用于 siRNA 和 shRNA 递送的基于纳米医学的 HuR 靶向方法的列表,并为基于纳米载体的 HuR 靶向提供了巨大的潜在治疗益处及其治疗 LC 患者的前景的理由。

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Drug delivery approaches for HuR-targeted therapy for lung cancer.用于肺癌的 HuR 靶向治疗的药物递送方法。
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