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整合素αvβ3作为胶质母细胞瘤的治疗靶点:回归未来?

Integrin-αvβ3 as a Therapeutic Target in Glioblastoma: Back to the Future?

作者信息

Echavidre William, Picco Vincent, Faraggi Marc, Montemagno Christopher

机构信息

Département de Biologie Médicale, Centre Scientifique de Monaco, 98000 Monaco, Monaco.

Nuclear Medicine Department, Centre Hospitalier Princesse Grace, 98000 Monaco, Monaco.

出版信息

Pharmaceutics. 2022 May 13;14(5):1053. doi: 10.3390/pharmaceutics14051053.

DOI:10.3390/pharmaceutics14051053
PMID:35631639
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9144720/
Abstract

Glioblastoma (GBM), the most common primary malignant brain tumor, is associated with a dismal prognosis. Standard therapies including maximal surgical resection, radiotherapy, and temozolomide chemotherapy remain poorly efficient. Improving GBM treatment modalities is, therefore, a paramount challenge for researchers and clinicians. GBMs exhibit the hallmark feature of aggressive invasion into the surrounding tissue. Among cell surface receptors involved in this process, members of the integrin family are known to be key actors of GBM invasion. Upregulation of integrins was reported in both tumor and stromal cells, making them a suitable target for innovative therapies targeting integrins in GBM patients, as their impairment disrupts tumor cell proliferation and invasive capacities. Among them, integrin-αvβ3 expression correlates with high-grade GBM. Driven by a plethora of preclinical biological studies, antagonists of αvβ3 rapidly became attractive therapeutic candidates to impair GBM tumorigenesis. In this perspective, the advent of nuclear medicine is currently one of the greatest components of the theranostic concept in both preclinical and clinical research fields. In this review, we provided an overview of αvβ3 expression in GBM to emphasize the therapeutic agents developed. Advanced current and future developments in the theranostic field targeting αvβ3 are finally discussed.

摘要

胶质母细胞瘤(GBM)是最常见的原发性恶性脑肿瘤,预后极差。包括最大程度手术切除、放疗和替莫唑胺化疗在内的标准治疗方法仍然效果不佳。因此,改善GBM的治疗方式是研究人员和临床医生面临的首要挑战。GBM具有侵袭周围组织的典型特征。在参与这一过程的细胞表面受体中,整合素家族成员是GBM侵袭的关键因素。整合素在肿瘤细胞和基质细胞中均有上调,这使其成为针对GBM患者整合素的创新疗法的合适靶点,因为对其进行抑制会破坏肿瘤细胞的增殖和侵袭能力。其中,整合素αvβ3的表达与高级别GBM相关。在大量临床前生物学研究的推动下,αvβ3拮抗剂迅速成为抑制GBM肿瘤发生的有吸引力的治疗候选药物。从这个角度来看,核医学的出现目前是临床前和临床研究领域治疗诊断概念的最大组成部分之一。在这篇综述中,我们概述了GBM中αvβ3的表达,以强调已开发的治疗药物。最后讨论了针对αvβ3的治疗诊断领域当前和未来的先进发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a360/9144720/45da06a6bd86/pharmaceutics-14-01053-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a360/9144720/45da06a6bd86/pharmaceutics-14-01053-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a360/9144720/45da06a6bd86/pharmaceutics-14-01053-g001.jpg

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